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Enzyme Nomenclature
Information on EC 1.6.3.1 - NAD(P)H oxidase (H2O2-forming)
Word Map on EC 1.6.3.1
- 1.6.3.1
- vascular
- endothelial
-
neutrophil
-
p22phox
- angiotensin
- dysfunction
- inflammation
- artery
- injury
- hypertension
- apocynin
-
oxidases
- diabetes
- cardiovascular
- dinucleotide
- nicotinamide
- atherosclerosis
- macrophage
- granulomatous
- aortic
- diphenyleneiodonium
- monocyte
-
chemiluminescence
-
mapks
-
ii-induced
- iodonium
-
diphenylene
-
phorbol
-
flavocytochrome
-
endothelium-dependent
-
oxidase-derived
- xanthine
- dihydroethidium
-
nitrotyrosine
- medicine
-
oxidase-dependent
-
microbicidal
-
nadph-oxidase
-
tempol
-
renin-angiotensin
- lucigenin
-
ros-dependent
- losartan
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lucigenin-enhanced
-
oxidase-mediated
- tiron
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non-phagocytic
- agriculture
- synthesis
-
h2o2-generating
- thyroperoxidase
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organification
- industry
-
ros-generating
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
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EC NUMBER 
COMMENTARY 
1.6.3.1
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RECOMMENDED NAME
GeneOntology No.
NAD(P)H oxidase (H2O2-forming)
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
NAD(P)H + H+ + O2 = NAD(P)+ + H2O2
model of electron transport from NADPH to the terminal electron acceptor O2
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NAD(P)H + H+ + O2 = NAD(P)+ + H2O2
flavoprotein; Requires FAD, heme and calcium. When calcium is present, this transmembrane glycoprotein generates H2O2 by transfering electrons from intracellular NAD(P)H to extracellular molecular oxygen. The electron bridge within the enzyme contains one molecule of FAD and probably two heme groups. This flavoprotein is expressed at the apical membrane of thyrocytes, and provides H2O2 for the thyroid peroxidase-catalysed biosynthesis of thyroid hormones
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NAD(P)H + H+ + O2 = NAD(P)+ + H2O2
in stable conformation, the active site adopts a closed conformation not allowing the substrate to bind. In presence of urea, an open conformation of the active site with 0.9 nm distance between the indole ring of W47 and the isoalloxazine ring of FMN412 is favored
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NAD(P)H + H+ + O2 = NAD(P)+ + H2O2
a cytosolic C-terminal dehydrogenase domain includes an FAD cofactor and an NADPH substrate binding site. On activation, electrons are transferred from NADPH to FAD and across the membrane, via heme irons, to molecular oxygen, thus producing superoxide anion, which can be dismutated into hydrogen peroxide
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
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-
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redox reaction
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-
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reduction
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SYSTEMATIC NAME
IUBMB Comments
NAD(P)H:oxygen oxidoreductase (H2O2-forming)
Requires FAD, heme and calcium. When calcium is present, this transmembrane glycoprotein generates H2O2 by transfering electrons from intracellular NAD(P)H to extracellular molecular oxygen. The electron bridge within the enzyme contains one molecule of FAD and probably two heme groups. This flavoprotein is expressed at the apical membrane of thyrocytes, and provides H2O2 for the thyroid peroxidase-catalysed biosynthesis of thyroid hormones.
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CAS REGISTRY NUMBER
COMMENTARY
9032-22-8
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
high sequence similarities to mammalian proteins
UniProt
rice pathogen, which undergoes an oxidative blast of its own during plant infection
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636490, 636501, 658889, 659332, 659626, 659956, 671246, 671829, 673788, 684695, 684771, 684779, 684781, 684859, 684866, 684872, 684904, 684970, 685016, 685277, 685410, 685793, 685998, 686126, 686418, 686520, 686556, 686848, 686879, 686880, 687050, 687587, 687620, 687649, 687674, 687742, 688206, 688216, 688583, 688599, 688605, 688753, 689213, 696030, 696573, 699176, 699287, 700052, 710782, 710897, 711166, 711688, 711763, 712075, 712673, 712711, 712713, 713338, 713360, 724704, 724778, 726081
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dual NADPH oxidases/peroxidases, Duox1 and Duox2. Regulation of expression by immunomodulatory Th1 and Th2 cytokines
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isoforms Duox1, Duox2, stable transfection in HEK293 and Chinese hamster ovary cells. Enzymes demonstrate a functional NADPH/Ca2+-dependent H2O2-generating activity. Human Duox2 is more active than human Duox1, but only half as active as its porcine counterpart
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multicomponent NADPH-oxidase consisting of a heterodimeric flavocytochrome b558, localized in the membrane and at least two cytosolic components p47-phox and p67-phox, enzyme plays a role in chronic granulomatous diseases, enzyme system is activated upon exposure to the appropriate stimuli leading to assembly in the plasma membrane of membrane-bound and cytosolic components
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674633, 684345, 684358, 684361, 684500, 684839, 685335, 685345, 685384, 685878, 685971, 685975, 685982, 686030, 686113, 686115, 686878, 687451, 687674, 687798, 687930, 688150, 688219, 688531, 688583, 688597, 689225, 690084, 690131, 690132, 690180, 697153, 697415, 698160, 701019, 710782, 710816, 711090, 711688, 711698, 711763, 711828, 712573, 713338, 725065
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wild-type, Cu,Zn-superoxide dismutase transgenic, and NAD(P)H oxidase-knockout mice placed on a normal or high cholesterol diet
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671217, 672959, 673106, 675531, 684269, 684343, 684364, 684977, 685873, 685888, 686306, 686562, 686602, 686616, 686848, 686859, 686862, 686883, 687050, 687051, 687053, 688446, 688530, 688531, 688550, 688627, 688711, 689235, 699700, 700427, 711166, 711645, 711688, 711731, 711856, 712062, 712826, 713366, 713491, 725062
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enzymes xanthine oxidase and xanthine dehydrogenase catalyze NADH oxidation, generating superoxide radicals
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transgenic rats harboring the mouse renin transgene and exhibiting elevated tissue angiotensin II levels
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isoforms Duox1, Duox2, stable transfection in HEK293 and Chinese hamster ovary cells. Enzymes demonstrate a functional NADPH/Ca2+-dependent H2O2-generating activity. Human Duox2 is only half as active as its porcine counterpart
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
additional information
malfunction
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the inhibition of NAD(P)H oxidase-dependent nuclear factor-kappa B signaling reduces the increase in monocyte chemoattractant protein-1 production by glomerular endothelial cells induced by angiotensin II
malfunction
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the inhibition of NADPH oxidase may contribute to lowered rate of renal gluconeogenesis, probably due to decreasing phosphoenolpyruvate carboxykinase activity
malfunction
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the inhibition of NADPH oxidase may contribute to lowered rate of renal gluconeogenesis, probably due to decreasing phosphoenolpyruvate carboxykinase activity
malfunction
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inhibition of NAD(P)H oxidase abolishes endothelial dysfunction in AMP-activated protein kinase alpha2-deficient mice
malfunction
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lentiviral silencing of Nox4 in an Ang2-sufficient bEnd cell line decreases Ang2 mRNA levels and greatly impairs hemangioma growth in vivo
malfunction
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isozyme Nox4 is involved in a variety of diseases such as idiopathic pulmonary fibrosis, pulmonary arterial hypertension, diabetic nephropathy, and complications such as diabetic cardiomyopathy and neuropathy and retinopathy or cancers like metastatic renal cell carcinoma
malfunction
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mice deficient in NOX4 of either sex, but not those deficient for NOX1 or NOX2, are largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia
malfunction
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NAD(P)H oxidase inhibition by apocynin might suppress reactive oxygen species production and confer neuroprotection in premature infants with intraventricular hemorrhage
malfunction
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DelTASsnox1 strains have reduced reactive oxygen species levels, are unable to develop sclerotia, and unexpectedly correlate with significantly reduced oxalate production. Inactivation of the Nox2 gene results in limited sclerotial development, but the organism remains fully pathogenic
malfunction
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excessive NADPH oxidase activation and reactive oxygen species overproduction are believed to participate in disorders such as joint, lung, vascular and intestinal inflammation
malfunction
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in pathological circumstances, excess Nox2 can lead to oxidative stress and disease development. NOX2 V204A mutant is a competitive inhibitor of wild-type p67phox. Binding of the PB1 domain of NOX2 to p40phox is abolished by a K355A mutation in NOX2. Depletion or mutation of p40phox impairs reactive oxygen species production in neutrophils and endothelial cells. Upregulation of Nox1 can lead to oxidative stress in the cardiovascular system
malfunction
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blockade of NAD(P)H oxidase with apocynin or superoxide dismutationwith PEG-SOD prevents the increment in superoxide and changes in P-eNOSThr495 observed during apamin and triarylmethane-34 application
malfunction
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specific inhibition of NOX by transfection of siRNA against p22phox mRNA effectively blocks low-density lipoprotein- or glycated low-density lipoprotein-induced increases in p22phox, NOX4, PAI-1, and HSF1 in wild-type mouse embryonic fibroblasts
malfunction
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specific inhibition of NOX by transfection of siRNA against p22phox mRNA effectively blocks low-density lipoprotein- or glycated low-density lipoprotein-induced increases in p22phox, NOX4, PAI-1, and HSF1 in wild-type mouse embryonic fibroblasts
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malfunction
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blockade of NAD(P)H oxidase with apocynin or superoxide dismutationwith PEG-SOD prevents the increment in superoxide and changes in P-eNOSThr495 observed during apamin and triarylmethane-34 application
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malfunction
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DelTASsnox1 strains have reduced reactive oxygen species levels, are unable to develop sclerotia, and unexpectedly correlate with significantly reduced oxalate production. Inactivation of the Nox2 gene results in limited sclerotial development, but the organism remains fully pathogenic
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metabolism
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tight regulation, critical to avoid excessive production of deleterious superoxide, is evident from the large number of proteins involved in oxidase assembly. These include Nox2 itself, p22phox, p47phox, p67phox, and p40phox, all essential subunits whose mutations can cause CGD Also crucial is Rac GTPase, which binds p67phox and the dehydrogenase domain of Nox2. In the resting state, Nox2 and p22phox form an inactive membrane complex known as cytochrome b558. Product superoxide is the first reactive oxygen species in a cascade of metabolites including hydrogen peroxide and peroxynitrite
metabolism
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mechanisms involved in the control of NO production involving the enzyme, NADPHox-mediated superoxide formation is involved in the inhibition of NO production, overview
metabolism
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mechanisms involved in the control of NO production involving the enzyme, NADPHox-mediated superoxide formation is involved in the inhibition of NO production, overview
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physiological function
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cathepsin L-derived endostatin, if excessive, may result in endothelial dysfunction through enhanced production of O2- due to NAD(P)H oxidase activation
physiological function
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cardiovascular NAD(P)H oxidases play important roles in physiological processes such as blood pressure regulation as well as pathophysiological events including hypertension and atherosclerosis
physiological function
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cardiovascular NAD(P)H oxidases play important roles in physiological processes such as blood pressure regulation as well as pathophysiological events including hypertension and atherosclerosis
physiological function
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cardiovascular NAD(P)H oxidases play important roles in physiological processes such as blood pressure regulation as well as pathophysiological events including hypertension and atherosclerosis
physiological function
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increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes
physiological function
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NAD(P)H oxidase-derived reactive oxygen species play a role in the development and progression of atherosclerosis
physiological function
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NAD(P)H oxidase is the main source of reactive oxygen species in diabetic podocytes and their production contributes to the development of diabetic nephropathy
physiological function
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NADPH oxidase is a major source of reactive oxygen species in aortas of spontaneously hypertensive rats
physiological function
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NAD(P)H oxidase is the major source of reactive oxygen species generation in the vasculature in response to high glucose and advanced glycation end-products. NAD(P)H oxidase in phagocytic cells releases reactive oxygen species as a defense against pathogens. Activation of NAD(P)H oxidase in diabetes leads to a cascade of reactive oxygen species production and impaired antioxidant defenses. In early stages of diabetes, NAD(P)H oxidase-derived reactive oxygen species may serve as intracellular mediators to regulate redox-sensitive transcription factors (e.g. Nrf2) involved in adaptive responses to oxidative stress
physiological function
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NAD(P)H oxidase is the major source of reactive oxygen species generation in the vasculature in response to high glucose and advanced glycation end-products. NAD(P)H oxidase in phagocytic cells releases reactive oxygen species as a defense against pathogens. Activation of NAD(P)H oxidase in diabetes leads to a cascade of reactive oxygen species production and impaired antioxidant defenses. In early stages of diabetes, NAD(P)H oxidase-derived reactive oxygen species may serve as intracellular mediators to regulate redox-sensitive transcription factors (e.g. Nrf2) involved in adaptive responses to oxidative stress
physiological function
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NAD(P)H oxidase is the major source of reactive oxygen species generation in the vasculature in response to high glucose and advanced glycation end-products. NAD(P)H oxidase in phagocytic cells releases reactive oxygen species as a defense against pathogens. Activation of NAD(P)H oxidase in diabetes leads to a cascade of reactive oxygen species production and impaired antioxidant defenses. In early stages of diabetes, NAD(P)H oxidase-derived reactive oxygen species may serve as intracellular mediators to regulate redox-sensitive transcription factors (e.g. Nrf2) involved in adaptive responses to oxidative stress
physiological function
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NAD(P)H oxidase is the major source of reactive oxygen species generation in the vasculature in response to high glucose and advanced glycation end-products. NAD(P)H oxidase in phagocytic cells releases reactive oxygen species as a defense against pathogens. Activation of NAD(P)H oxidase in diabetes leads to a cascade of reactive oxygen species production and impaired antioxidant defenses. In early stages of diabetes, NAD(P)H oxidase-derived reactive oxygen species may serve as intracellular mediators to regulate redox-sensitive transcription factors (e.g. Nrf2) involved in adaptive responses to oxidative stress
physiological function
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the 28000 Da NOX4 isoform has a key role in toll-like receptor 4-mediated apoptosis during renal ischemia/reperfusion injury. NOX4 controls Jun N-terminal kinase-mediated renal tubule cell apoptosis induced by hypoxia
physiological function
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NAD(P)H oxidase activity promotes cellular hypoxia (nonspecific reduction of metronidazole)
physiological function
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in skeletal muscle and in heart the NADPH oxidase system is mainly involved in oxidative stress
physiological function
while macula densa cells express the NOX2 and NOX4 isoforms, NOX 2 is primarily responsible for NaCl-induced O2- generation
physiological function
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oxidative stress is dependent on the upregulation of NAD(P)H oxidase 4, a reactive oxygen species Nox homologue, triggering endoplasmic reticulum stress. The endoplasmic reticulum stress pathway through activation of Nox4 by integrins alpha1beta1 plays a key role in 3-deoxyglucosone-collagen-induced caspase-3 activation, which may play an important role in the pathogenesis of diabetic wounds
physiological function
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NAD(P)H derived superoxide generation is the underlying cause of vasoactive dysfunction in hyperglycemic Goto-Kakizaki arteries
physiological function
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germinal matrix hemorrhage-intraventricular hemorrhage, by induction of NAD(P)H oxidases, may cause oxidative/nitrosative stress contributing to brain injuries. Activation of NAD(P)H oxidase is the predominant mechanism of free-radical generation in pups with intraventricular hemorrhage
physiological function
Nox1 relates production of reactive oxygen species to specific biocontrol activity against Pythium ultimum, but not Botrytis cinerea or Rhizoctonia solani
physiological function
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fungal NADPH oxidases are required for pathogenic development and are consistent with the importance of reactive oxygen species regulation in the successful pathogenesis of Sclerotinia sclerotiorum. Central role for SsNox1 in both virulence and pathogenic (sclerotial) development
physiological function
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reactive oxygen species production by the phagocyte NADPH oxidase is essential for host defenses against pathogens. Reactive oxygen species are very reactive with biological molecules such as lipids, proteins and DNA, potentially resulting in cell dysfunction and tissue insult. Enzyme component P47phox is phosphorylated on multiple sites located in its carboxy-terminal portion, including serines 303-379, which play a central role in NADPH oxidase activation and regulation. In human neutrophils, various protein kinases have been implicated in the activation of NADPH oxidase, among which the PKC and MAP kinase families appear to play a major role
physiological function
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NADPH oxidase enzymes are critical mediators of cardiovascular physiology and pathophysiology. They are expressed in virtually all cardiovascular cells, and regulate such diverse functions as differentiation, proliferation, apoptosis, senescence, inflammatory responses and oxygen sensing. They target a number of important signaling molecules, including kinases, phosphatases, transcription factors, ion channels, and proteins that regulate the cytoskeleton. On activation, Nox2 uses NADPH to reduce molecular oxygen to superoxide anion, which, in concert with its metabolites, is used by phagocytes to destroy invading microorganisms. Nox organizers include both p47phox and its homologue, Noxo1, whereas Nox activators comprise p67phox and the structurally similar Noxa1. Because Nox2 and Nox1 are closely related, both enzymes can be activated in transfected cells by various organizer and activator pairs. Nox1 plays a host defensive role in colon epithelium. primary biochemical function of vascular Nox1 is superoxide production, which is then rapidly converted to hydrogen peroxide. The moderate physiological activity of Nox1, compared with the phagocytic Nox2, can be attributed to its low expression as well as specific regulatory subunits and signaling cascades. Nox4 is a constitutively active enzyme mostly regulated by transcription. Role of enzyme complex component p22phox, detailed overview. Nox4 can produce a higher hydrogen peroxide to superoxide ratio than Nox1 and Nox2. Isozyme Nox5S may be constitutively active or be a competitive inhibitor of calcium-dependent activation when present in the same tetrameric complex as Nox5L
physiological function
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blockade of small-conductance and intermediate-conductance Ca2+-activated K+ channels activates NAD(P)H oxidase-dependent superoxide formation, which leads to inhibition of NO release through P-eNOSThr495
physiological function
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regulatory role of NADPH oxidase in glycated low-density lipoprotein-induced upregulation of plasminogen activator inhibitor-1 and heat shock factor-1 in mouse embryo fibroblasts and diabetic mice, overview. NOX4 plays a crucial role in glycated low-density lipoprotein-induced expression of HSF1andPAI-1 in mouse fibroblasts
physiological function
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the activity of NOX5 appears to be regulated by a self-contained Ca2+ binding domain, the conformational change of the domain upon Ca2+ binding is essential for domain-domain interaction and superoxide production
physiological function
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NAD(P)H oxidase activity promotes cellular hypoxia (nonspecific reduction of metronidazole)
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physiological function
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regulatory role of NADPH oxidase in glycated low-density lipoprotein-induced upregulation of plasminogen activator inhibitor-1 and heat shock factor-1 in mouse embryo fibroblasts and diabetic mice, overview. NOX4 plays a crucial role in glycated low-density lipoprotein-induced expression of HSF1andPAI-1 in mouse fibroblasts
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physiological function
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blockade of small-conductance and intermediate-conductance Ca2+-activated K+ channels activates NAD(P)H oxidase-dependent superoxide formation, which leads to inhibition of NO release through P-eNOSThr495
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physiological function
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fungal NADPH oxidases are required for pathogenic development and are consistent with the importance of reactive oxygen species regulation in the successful pathogenesis of Sclerotinia sclerotiorum. Central role for SsNox1 in both virulence and pathogenic (sclerotial) development
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physiological function
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Nox1 relates production of reactive oxygen species to specific biocontrol activity against Pythium ultimum, but not Botrytis cinerea or Rhizoctonia solani
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additional information
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for the activation of Nox enzymes, cytosolic regulatory components (Rac, p67phox, p47phox, and p40phox) are recruited into the integral membrane protein flavocytochrome b558, consisting of the catalytic subunits gp91phox and p22phox
additional information
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active phagocyte NADPH oxidase is a multicomponent enzyme complex composed of six proteins: p22phox (phox: phagocyte oxidase), gp91phox/NOX2, p47phox, p67phox, p40phox and the small G-protein Rac1 or Rac2
additional information
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Nox5 is similar to other Nox enzymes, with 6 transmembrane helices expected to bind 2 hemes and a cytosolic dehydrogenase domain including FAD and NADPH binding sites, but neither Nox5 isoform appears to require cytosolic subunits or p22phox. Presence of an additional cytosolic N-terminal segment, containing 4 calcium binding EF-hands in Nox5. Nox4 activity is constitutive, isozyme Nox4D appears to be fully active, although it lacks most of the transmembrane domain, it might retain activity by coupling to electron acceptors, such as cytochrome c in mitochondria, which might also be an alternative route of hydrogen peroxide formation by full-length Nox4. Nox4, Nox1 and Nox2 bind to p22phox, the interaction is abolished by mutation of heme-binding histidine 115. Nox2 is composed of two main domains of equal sizes with very different properties. The amino-terminal moiety includes six transmembrane alpha-helices I-VI connected by 5 loops A-E. Because both N- and C-termini are cytosolic, 3 loops are extracellular and include consensus asparagine glycosylation sites, whereas the other 2 are intracellular and accessible to cytosolic regulators. The cytosolic carboxy-terminal moiety of Nox2 constitutes a dehydrogenase domain that includes consensus binding sites for its NADPH substrate and FAD cofactor, activation domain of p67phox triggers FAD reduction by Nox2. A charge compensation mechanism, required to balance electron transport by Nox2 and sustain its activity, is provided by a voltage-gated proton channel8 and the chloride/proton antiporter ClC-3. The first SH3 domain of NOX2 increases oxidase activity, the NOX2 PB1 domain allows binding to p40phox. The C-terminal SH3 domain of p67phox of NOX2 is responsible for binding the proline-rich region of p47phox and therefore allows p67phox translocation to the membrane after activation. The C-terminal PB1 domain of p40phox interacts with the PB1 domain of p67phox. Nox1, like Nox2, associates with p22phox to form a membrane-bound cytochrome
additional information
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for the activation of Nox enzymes, cytosolic regulatory components (Rac, p67phox, p47phox, and p40phox) are recruited into the integral membrane protein flavocytochrome b558, consisting of the catalytic subunits gp91phox and p22phox
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
NADPH + H+ + O2
?
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the protein shows NADH-ubiquinone-1 oxidoreductase activity (EC 1.6.5.3), NADPH oxidase (EC 1.6.3.1) and NADPH-ubiquinone-1 oxidoreductase (EC 1.6.5.2) activities
-
-
?
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
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production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
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-
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NAD(P)H + H+ + O2
NAD(P)+ + H2O2
enzyme deficiency causes serious hypothyroidism
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NAD(P)H + H+ + O2
NAD(P)+ + H2O2
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production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
-
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
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NAD(P)H + H+ + O2
NAD(P)+ + H2O2
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production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
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-
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NAD(P)H + H+ + O2
NAD(P)+ + H2O2
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NAD(P)H oxidase transfers electrons across membranes to oxygen and generate superoxide anions which rapidly dismutate to hydrogen peroxide
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-
?
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
-
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
-
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
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enzyme is an important factor for the generation of reactive oxygen species in astrocytes, and the reactive oxygen species generated by enzyme play an essential role in astrocyte survival
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-
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NAD(P)H + H+ + O2
NAD(P)+ + H2O2
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production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
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NAD(P)H + H+ + O2
NAD(P)+ + H2O2
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
-
NADH + H+ + O2
NAD+ + H2O2
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2 electrons are transferred from cytosolic NADPH to FAD and in succession across the membrane, via redox changes in heme irons. Finally, each electron reduces a molecule of oxygen to a superoxide radical, which is subsequently released outside the cell or in a topologically equivalent compartment, such as a vesicle lumen
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-
?
NADH + H+ + O2
NAD+ + H2O2
-
oxidizes NADH and, less efficiently, NADPH
-
-
?
NADH + H+ + O2
NAD+ + H2O2
-
oxidizes NADH and, less efficiently, NADPH
-
-
?
NADH + H+ + O2
NAD+ + H2O2
activity with NADPH is much lower than with NADH
-
-
?
NADPH + H+ + O2
NADP+ + H2O2
-
-
-
-
?
NADPH + H+ + O2
NADP+ + H2O2
NOX3 is a relevant source of reactive oxygen species generation in the cochlear and vestibular systems. NOX3-dependent ROS generation might contribute to hearing loss and balance problems in response to toxic drugs
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-
?
NADPH + H+ + O2
NADP+ + H2O2
NOX3 is a relevant source of reactive oxygen species generation in the cochlear and vestibular systems. NOX3-dependent ROS generation might contribute to hearing loss and balance problems in response to ototoxic drugs
-
-
?
NADPH + H+ + O2
NADP+ + H2O2
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the active enzyme complex produces O2 radicals, which are converted into superoxide-derived oxidants such as H2O2, hydroxyl radicals, and peroxynitrite
-
-
?
NADPH + H+ + O2
NADP+ + H2O2
-
oxidizes NADH and, less efficiently, NADPH (2fold lower activity)
-
-
?
NADPH + H+ + O2
NADP+ + H2O2
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oxidizes NADH and, less efficiently, NADPH (2fold lower activity)
-
-
?
NADPH + H+ + O2
NADP+ + H2O2
activity with NADPH is much lower than with NADH
-
-
?
NADPH + O2
NADP+ + O2-
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enzyme is stimulated by phagocytizable particles
-
?
NADPH + O2
NADP+ + O2-
-
part of defense mechanism against a wide variety of bacteria
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?
NADPH + O2
NADP+ + O2-
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in pathological conditions where an increase in NADH concentration occurs, the NADH oxidation catalysed by xanthine dehydrogenase may constitute an important pathway for reactive oxygen species-mediated tissue injuries
-
-
?
NADPH + O2
NADP+ + O2-
-
reaction catalyzed by xanthine oxidase and xanthine dehydrogenase
-
-
?
additional information
?
-
-
lignin deposition induced by cellulose biosynthesis inhibition is regulated by JAR1-1 and NADPH oxidase-dependent signalling processes
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-
-
additional information
?
-
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enzyme provides hydrogen peroxide for iodine metabolism in the thyroid
-
-
-
additional information
?
-
-
direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappaB
-
-
-
additional information
?
-
-
the production of reactive oxygen species is initiated by the phygocyte NADPH oxidase
-
-
-
additional information
?
-
-
enzyme isoform Nox3 plays an integral role in insulin-induced p42/44 MAPK signal transmission and VEGF-A production
-
-
-
additional information
?
-
-
essential role of enzyme-generated reactive oxigen species in insulin-stimulated activation of hypoxia-inducible factor 1
-
-
-
additional information
?
-
-
formation of a complex consisting of enzyme, guanine exchange factor for Rac, betaPix, and enzyme organizer NoxO1 is a critical step in EGF-induced generation of reactive oxygen species
-
-
-
additional information
?
-
-
active NAD(P)H oxidase is required for vascular endothelial growth factor activation of phosphoinositide 3-kinase-Akt-forkhead, and p38 mitogen-activated kinase, but not extracellular signal-related kinase 1/2 or c-Jnu N-terminal kinase. The permissive role of NADPH oxidase on phosphoinositide 3-kinase-Akt-forkhead signaling is mediated at post-vascular endothelial growth factor receptor levels and involves the nonreceptor tyrosine kinase Src
-
-
-
additional information
?
-
-
NAD(P)H oxidase plays an essential role in maintaining basal levels of reactive oxygen species in NB-4 cells
-
-
-
additional information
?
-
-
subunit p40phox functions primarily to regulate Fcgamma receptor-induced NADPH oxidase activity rather than assembly of the enzyme, and stimulates superoxide production via a phosphoinositol 3-phosphate signal that increases after phagosome internalization
-
-
-
additional information
?
-
-
chronic granulomatous disease is a rare inherited immunodeficiency syndrome caused by mutations in four genes encoding essential nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex components
-
-
-
additional information
?
-
Duox NADPH oxidases generate hydrogen peroxide at the air-liquid interface of the respiratory tract and at apical membranes of thyroid follicular cells
-
-
-
additional information
?
-
-
NADPH oxidase mediates angiotensin II-stimulated protein synthesis downstream of the type 1 receptor AT1 in myometrium smooth muscle cells
-
-
-
additional information
?
-
-
the membrane-bound NADPH oxidase in phagocytes, gp91phox/Nox2, produces superoxide, a precursor of microbicidal oxidants, thereby playing a crucial role in host defense. Activation of gp91phox/Nox2 requires assembly with the cytosolic proteins p67phox and p47phox, each containing two SH3 domains. p67phox-SH3(N) specifically functions in gp91phox/Nox2 activation probably via facilitating oxidase assembly
-
-
-
additional information
?
-
-
the potent anti-inflammatory, cytokine interleukin-10, acts as a down-regulator of the Nox1-based oxidase in the colon, and suggests an important role of ROS derived from Nox1-based oxidase in the initiation of inflammatory responses of the colon
-
-
-
additional information
?
-
-
Nox4 can produce a higher hydrogen peroxide to superoxide ratio than Nox1 and Nox2. NOX2-produced superoxide can be released outside the cell when Nox2 is located at the plasma membrane, thus allowing it to intercept, e.g., with endothelial-derived nitric oxide before it reaches the adjacent smooth muscle cell layer in vessels
-
-
-
additional information
?
-
NOX1 generates superoxide when coexpressed with the p47(phox) and p67(phox) subunits of the phygocyte NADPH oxidase but not when expressed by itself
-
-
-
additional information
?
-
-
reactive oxygen species generated by the transverse tubule NADPH oxidase enzyme activate via redox modification the neighboring RyR1 Ca2+ release channels
-
-
-
additional information
?
-
-
angiotensin II-evoked expression of endothelin-1 in adventitial fibroblasts is mediated, at least in part, by NADPH oxidase. This mechanism stimulates collagen expression thereby implicating the adventitia as a potential contributor to the vascular pathophysiology associated with oxidative stress and vascular remodeling
-
-
-
additional information
?
-
-
superoxide anions play a key role in suppressing K +secretion during K+ restriction and isoform NoxII is involved in mediating the effect of low K +intake on renal K+ secretion and ROMK channel activity
-
-
-
additional information
?
-
-
decreased hepatic fibrosis after chronic CCl4 administration in mice with NADPH oxidase deficiency occurs in the setting of greater necrosis and inflammation but decreased apoptosis
-
-
-
additional information
?
-
-
NADPH oxidase is an important molecular sources responsible for superoxide overproduction after high-glucose exposure
-
-
-
additional information
?
-
-
NADPH oxidase may play a potential role in oxidative stress-induced arterial tetrahydrobiopterin and GTP cyclohydrolase I deficiency, resulting in endothelial dysfunction in Ins2Akita type 1 diabetic mice fed a high-cholesterol diet
-
-
-
additional information
?
-
-
isoform NOX-1 is required for sexual and asexual development, and normal hyphal growth, while isoform NOX-2 is specifically involved in sexual spore function. Regulatory subunit NOR-1 is required for NOX-1 and NOX-2 functions at different developmental stages
-
-
-
additional information
?
-
-
hypoosmotic swelling of cardiac myocytes activates volume-sensitive Cl- current via the angiotensin II-reactive oxygen species signalling cascade
-
-
-
additional information
?
-
-
enzyme-derived reactive oxigen species modulate cerebral vascular tone under physiological conditions
-
-
-
additional information
?
-
-
glucose-mediated down-regulation of protein kinase G-I expression in vascular smooth muscle cells occurs through protein kinase C-dependent activation of NAD(P)H oxidase derived superoxide production, contributing to diabetes-associated vessel dysfunctions
-
-
-
additional information
?
-
-
NAD(P)H oxidase/superoxide and RhoA/Rho kinase are involved in the interaction between alpha2-adrenoceptors and angiotensin II on renal vascular resistance by mediating signaling events downstream of the phospholipase C/protein kinase C/c-src pathway
-
-
-
additional information
?
-
-
involvement of reactive oxygen species from NADPH oxidase in cytokine induction of secretory phospholipase A2-IIA in astrocytes
-
-
-
additional information
?
-
-
L-carnitine inhibits angiotensin II increased NADPH oxidase activity and intracellular ROS levels in cardiac fibroblasts
-
-
-
additional information
?
-
-
the activated Nox enzyme complex generates superoxide from oxygen by utilizing NADPH as an electron donor, thereby leading to the formation of other species of reactive oxygen
-
-
-
additional information
?
-
-
the activated Nox enzyme complex generates superoxide from oxygen by utilizing NADPH as an electron donor, thereby leading to the formation of other species of reactive oxygen
-
-
-
additional information
?
-
-
calcium-dependent kinase CDPK5 induces phosphorylation of the catalytic subunit at resiude S82 and thereby regulates the oxidative burst
-
-
-
additional information
?
-
-
the initial burst of superoxide in response to wounding is mediated by isoform Strboh A
-
-
-
additional information
?
-
KOD1 (TkNOX) catalyzes oxidation of NADH and NADPH with oxygen from atmospheric air as an electron acceptor
-
-
-
additional information
?
-
-
plasma membrane NADPH oxidase participates in the Ni-induced production of reactive oxygen species, and Ca2+ may be involved in the oxidative stress induced by nickel in wheat roots
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
-
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
-
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
Q9NRD8
enzyme deficiency causes serious hypothyroidism
-
-
-
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
-
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
-
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
Q9NRD8
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
-
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
-
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
-
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
-
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
-
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
-
enzyme is an important factor for the generation of reactive oxygen species in astrocytes, and the reactive oxygen species generated by enzyme play an essential role in astrocyte survival
-
-
-
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
-
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
-
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
Q8HZK2
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
-
NADH + H+ + O2
NAD+ + H2O2
-
2 electrons are transferred from cytosolic NADPH to FAD and in succession across the membrane, via redox changes in heme irons. Finally, each electron reduces a molecule of oxygen to a superoxide radical, which is subsequently released outside the cell or in a topologically equivalent compartment, such as a vesicle lumen
-
-
?
NADPH + H+ + O2
NADP+ + H2O2
Q672J9
NOX3 is a relevant source of reactive oxygen species generation in the cochlear and vestibular systems. NOX3-dependent ROS generation might contribute to hearing loss and balance problems in response to toxic drugs
-
-
?
NADPH + H+ + O2
NADP+ + H2O2
Q672K1
NOX3 is a relevant source of reactive oxygen species generation in the cochlear and vestibular systems. NOX3-dependent ROS generation might contribute to hearing loss and balance problems in response to ototoxic drugs
-
-
?
NADPH + O2
NADP+ + O2-
-
enzyme is stimulated by phagocytizable particles
-
?
NADPH + O2
NADP+ + O2-
-
part of defense mechanism against a wide variety of bacteria
-
?
NADPH + O2
NADP+ + O2-
-
in pathological conditions where an increase in NADH concentration occurs, the NADH oxidation catalysed by xanthine dehydrogenase may constitute an important pathway for reactive oxygen species-mediated tissue injuries
-
-
?
additional information
?
-
-
lignin deposition induced by cellulose biosynthesis inhibition is regulated by JAR1-1 and NADPH oxidase-dependent signalling processes
-
-
-
additional information
?
-
-
enzyme provides hydrogen peroxide for iodine metabolism in the thyroid
-
-
-
additional information
?
-
-
direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappaB
-
-
-
additional information
?
-
-
the production of reactive oxygen species is initiated by the phygocyte NADPH oxidase
-
-
-
additional information
?
-
-
enzyme isoform Nox3 plays an integral role in insulin-induced p42/44 MAPK signal transmission and VEGF-A production
-
-
-
additional information
?
-
-
essential role of enzyme-generated reactive oxigen species in insulin-stimulated activation of hypoxia-inducible factor 1
-
-
-
additional information
?
-
-
formation of a complex consisting of enzyme, guanine exchange factor for Rac, betaPix, and enzyme organizer NoxO1 is a critical step in EGF-induced generation of reactive oxygen species
-
-
-
additional information
?
-
-
active NAD(P)H oxidase is required for vascular endothelial growth factor activation of phosphoinositide 3-kinase-Akt-forkhead, and p38 mitogen-activated kinase, but not extracellular signal-related kinase 1/2 or c-Jnu N-terminal kinase. The permissive role of NADPH oxidase on phosphoinositide 3-kinase-Akt-forkhead signaling is mediated at post-vascular endothelial growth factor receptor levels and involves the nonreceptor tyrosine kinase Src
-
-
-
additional information
?
-
-
NAD(P)H oxidase plays an essential role in maintaining basal levels of reactive oxygen species in NB-4 cells
-
-
-
additional information
?
-
-
subunit p40phox functions primarily to regulate Fcgamma receptor-induced NADPH oxidase activity rather than assembly of the enzyme, and stimulates superoxide production via a phosphoinositol 3-phosphate signal that increases after phagosome internalization
-
-
-
additional information
?
-
-
chronic granulomatous disease is a rare inherited immunodeficiency syndrome caused by mutations in four genes encoding essential nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex components
-
-
-
additional information
?
-
Q9NRD9
Duox NADPH oxidases generate hydrogen peroxide at the air-liquid interface of the respiratory tract and at apical membranes of thyroid follicular cells
-
-
-
additional information
?
-
-
NADPH oxidase mediates angiotensin II-stimulated protein synthesis downstream of the type 1 receptor AT1 in myometrium smooth muscle cells
-
-
-
additional information
?
-
-
the membrane-bound NADPH oxidase in phagocytes, gp91phox/Nox2, produces superoxide, a precursor of microbicidal oxidants, thereby playing a crucial role in host defense. Activation of gp91phox/Nox2 requires assembly with the cytosolic proteins p67phox and p47phox, each containing two SH3 domains. p67phox-SH3(N) specifically functions in gp91phox/Nox2 activation probably via facilitating oxidase assembly
-
-
-
additional information
?
-
-
the potent anti-inflammatory, cytokine interleukin-10, acts as a down-regulator of the Nox1-based oxidase in the colon, and suggests an important role of ROS derived from Nox1-based oxidase in the initiation of inflammatory responses of the colon
-
-
-
additional information
?
-
-
Nox4 can produce a higher hydrogen peroxide to superoxide ratio than Nox1 and Nox2. NOX2-produced superoxide can be released outside the cell when Nox2 is located at the plasma membrane, thus allowing it to intercept, e.g., with endothelial-derived nitric oxide before it reaches the adjacent smooth muscle cell layer in vessels
-
-
-
additional information
?
-
-
reactive oxygen species generated by the transverse tubule NADPH oxidase enzyme activate via redox modification the neighboring RyR1 Ca2+ release channels
-
-
-
additional information
?
-
-
angiotensin II-evoked expression of endothelin-1 in adventitial fibroblasts is mediated, at least in part, by NADPH oxidase. This mechanism stimulates collagen expression thereby implicating the adventitia as a potential contributor to the vascular pathophysiology associated with oxidative stress and vascular remodeling
-
-
-
additional information
?
-
-
superoxide anions play a key role in suppressing K +secretion during K+ restriction and isoform NoxII is involved in mediating the effect of low K +intake on renal K+ secretion and ROMK channel activity
-
-
-
additional information
?
-
-
decreased hepatic fibrosis after chronic CCl4 administration in mice with NADPH oxidase deficiency occurs in the setting of greater necrosis and inflammation but decreased apoptosis
-
-
-
additional information
?
-
-
NADPH oxidase is an important molecular sources responsible for superoxide overproduction after high-glucose exposure
-
-
-
additional information
?
-
-
NADPH oxidase may play a potential role in oxidative stress-induced arterial tetrahydrobiopterin and GTP cyclohydrolase I deficiency, resulting in endothelial dysfunction in Ins2Akita type 1 diabetic mice fed a high-cholesterol diet
-
-
-
additional information
?
-
-
isoform NOX-1 is required for sexual and asexual development, and normal hyphal growth, while isoform NOX-2 is specifically involved in sexual spore function. Regulatory subunit NOR-1 is required for NOX-1 and NOX-2 functions at different developmental stages
-
-
-
additional information
?
-
-
hypoosmotic swelling of cardiac myocytes activates volume-sensitive Cl- current via the angiotensin II-reactive oxygen species signalling cascade
-
-
-
additional information
?
-
-
enzyme-derived reactive oxigen species modulate cerebral vascular tone under physiological conditions
-
-
-
additional information
?
-
-
glucose-mediated down-regulation of protein kinase G-I expression in vascular smooth muscle cells occurs through protein kinase C-dependent activation of NAD(P)H oxidase derived superoxide production, contributing to diabetes-associated vessel dysfunctions
-
-
-
additional information
?
-
-
NAD(P)H oxidase/superoxide and RhoA/Rho kinase are involved in the interaction between alpha2-adrenoceptors and angiotensin II on renal vascular resistance by mediating signaling events downstream of the phospholipase C/protein kinase C/c-src pathway
-
-
-
additional information
?
-
-
involvement of reactive oxygen species from NADPH oxidase in cytokine induction of secretory phospholipase A2-IIA in astrocytes
-
-
-
additional information
?
-
-
L-carnitine inhibits angiotensin II increased NADPH oxidase activity and intracellular ROS levels in cardiac fibroblasts
-
-
-
additional information
?
-
-
the activated Nox enzyme complex generates superoxide from oxygen by utilizing NADPH as an electron donor, thereby leading to the formation of other species of reactive oxygen
-
-
-
additional information
?
-
-
the activated Nox enzyme complex generates superoxide from oxygen by utilizing NADPH as an electron donor, thereby leading to the formation of other species of reactive oxygen
-
-
-
additional information
?
-
-
calcium-dependent kinase CDPK5 induces phosphorylation of the catalytic subunit at resiude S82 and thereby regulates the oxidative burst
-
-
-
additional information
?
-
-
the initial burst of superoxide in response to wounding is mediated by isoform Strboh A
-
-
-
additional information
?
-
Q5JFZ8
KOD1 (TkNOX) catalyzes oxidation of NADH and NADPH with oxygen from atmospheric air as an electron acceptor
-
-
-
additional information
?
-
-
plasma membrane NADPH oxidase participates in the Ni-induced production of reactive oxygen species, and Ca2+ may be involved in the oxidative stress induced by nickel in wheat roots
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
-
contains 1 FAD molecule/subunit, the enzyme requires the presence of FAD as cofactor
FAD
Nox1 protein reveals the presence of six transmembrane domains and one FAD/NADPH binding cytosolic domain
FAD
-
a dehydrogenase domain is binding FAD and NADPH, Nox1, Nox2, and Nox4 requires FAD and NADPH. Nox5 is similar to other Nox enzymes, with 6 transmembrane helices expected to bind 2 hemes and a cytosolic dehydrogenase domain including FAD and NADPH binding sites
heme
-
4 conserved histidine residues in transmembrane helices III and V, thought to coordinate 2 heme molecules, mutation of these histidines abolishes binding to p22phox
NADH
preference to NADPH versus NADH as an electron donor during oxygen reduction; preference to NADPH versus NADH as an electron donor during oxygen reduction
NADPH
Nox1 protein reveals the presence of six transmembrane domains and one FAD/NADPH binding cytosolic domain
NADPH
-
a dehydrogenase domain is binding FAD and NADPH, Nox1, Nox2, and Nox4 requires FAD and NADPH. Nox5 is similar to other Nox enzymes, with 6 transmembrane helices expected to bind 2 hemes and a cytosolic dehydrogenase domain including FAD and NADPH binding sites
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Cd2+
Ni2+
-
treatment of root with Ni2+ results in significant increase in level of membrane lipid peroxidation, content of H2O2, the production rate of superoxide radicals and the activity of the PM NADPH oxidase. Effects of Ni2+ are inhibitied by treratment with enzyme inhibitors diphenylene idonium, imidazole and pyridine
Zn2+
additional information
Ca2+
-
Ca2+-induced conformation change of NADPH oxidase 5 N-terminus leads to enzyme activation through an intramolecular interaction
Ca2+
-
store-operated Ca2+ entry is required at the beginning of NADPH oxidase activation in response to N-formyl-L-methionyl-L-leucyl-Lphenylalanine in neutrophil-like HL-60 cells. When extracellular Ca2+ is initially removed, early addition of Ca2+ after stimulation causes a complete restoration of Ca2+ entry and H2O2production. Both Ca2+ entry and H2O2 production are decreased by purported SOCE blockers, 2-aminoethoxydiphenyl borane (2-APB) and SK&F 96365. Ca2+ influx in HL-60 cells relies on different membrane transient receptor potential canonical channels and Orai1 for allowing NADPH oxidase activation
Ca2+
-
an increase in cytosolic calcium concentration triggers high superoxide production by Nox5. Calcium induces binding of the N-terminal domain of Nox5 to the dehydrogenase domain, thus relieving autoinhibition. Two mechanisms may increase Nox5 sensitivity, allowing activation by resting calcium concentrations: (1) calcium-dependent binding of calmodulin to another site in the dehydrogenase domain157 and (2) phosphorylation of serine and threonine residues by protein kinase C and calcium/calmodulin-dependent kinase II
Ca2+
-
the activity of NOX5 appears to be regulated by a self-contained Ca2+ binding domain, residues 1-169, the conformational change of the domain upon Ca2+ binding is essential for domain-domain interaction and superoxide production. Ca2+ binding to Ca2+ binding domain induces a conformational change that exposes hydrophobic patches and increases the quenching accessibilities of its Trp residues and 5-((((2-iodoacetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid at Cys107, no significant changes in the secondary structures of Ca2+ binding domain upon metal binding. The C-terminal half of the domain has a higher Ca2+ binding affinity, a higher chemical stability, and a slow Ca2+ dissociation. the N- and C-terminal halves of the domain are not completely structurally independent
Ca2+
-
Ca2+ may regulate the interaction between cytosolic regulator subunit Rac and the N-terminal extension of the catalytic subunit in a dynamic manner
Ca2+
-
half maximal activity with 0.0001 mM Ca2+; regulates enzyme activity; required for full activity
Ca2+
-
a Ca2+/NADPH-dependent H2O2 generating system is associated with isoform Duox2 protein expression
Ca2+
-
pretreatments of wheat seedlings with Ca2+ channel blockers inhibits Ni-induced increase in plasma membrane NADPH oxidase activity
additional information
-
Mg2+ cannot substitute for Ca2+, metal binding/dissociation kinetics, overview
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(-)-epicatechin
-
serves as prodrug for conversion into apocynin-like NAD(P)H oxidase inhibitors
(-)-epicatechin glucuronide
-
acts both as a superoxide anion scavenger,and inhibitory to NAD(P)H oxidase, with apocynin-like mode of NADPH oxidase inhibition
(-)-epigallocatechin-3-O-(3-O-methyl)-gallate
-
inhibition of intracellular reactive oxygen species generation
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundec-3-yn-1-yl]octahydro-2,2'-bifuran-5-yl]dodec-4-yn-1-ol
-
-
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]dodecan-1-ol
-
-
(1R,1'R)-1,1'-((2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyl)-bis-(6-(4-n-butylphenoxy)hex-3-yn-1-ol)
-
-
(1R,1'R)-1,1'-((2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyl)-bis-(6-(4-n-butylphenoxy)hexan-1-ol)
-
-
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
-
complete inhibition at 0.01 mM
(3Z)-3-(3,4-dihydroxybenzylidene)-5-nitro-1,3-dihydro-2H-indol-2-one
-
complete inhibition at 0.01 mM
(3Z)-3-[4-hydroxy-3,5-di(propan-2-yl)benzylidene]-1,3-dihydro-2H-indol-2-one
-
complete inhibition at 0.01 mM
(5'Z)-5'-[(4-heptyl-5-methyl-1H-pyrrol-2-yl)methylidene]-4'-methoxy-1H,5'H-2,2'-bipyrrole
-
i.e. PG-L-1, prodigosin analogue, a red pigment isolated from marine bacterial strain. Significant inhibition of superoxide anion production by phorbol 12-myristate 13-acetate stimulated RAW 264.7 cells. (5'Z)-5'-[(4-heptyl-5-methyl-1H-pyrrol-2-yl)methylidene]-4'-methoxy-1H,5'H-2,2'-bipyrrole strongly inhibits the association of subunits p47phox and Rac in the plasma membrane
1-(2-chlorobenzyl)-4-methyl-5-[3-(2-oxopyrrolidin-1-yl)propyl]-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
1-(4-fluorobenzyl)-5-[2-(1H-indol-3-yl)ethyl]-4-methyl-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
1-acetyl-2-(2-chlorophenyl)-4-methyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
1-acetyl-4-methyl-2-(2-methylphenyl)-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
1-acetyl-4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
1-[(3-methoxyphenyl)acetyl]-4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
15-cis-(4-propyl-cyclohexyl)-16,17,18,19,20-pentanor-9-deoxy-9alpha,6-nitrilo-prostaglandin F1 methyl ester
-
0.021 mM, 50% inhibition of the enzyme in neutrophils possible due to scavenging of O2-, inhibition of SDS-induced activation in cell free extracts, 0.22 mM, 50% inhibition
2,3,8,9-tetrahydroxy-5-(2-hydroxy-5-nitrobenzyl)phenanthridin-6(5H)-one
-
complete inhibition at 0.01 mM
2,3,8,9-tetrahydroxy-5-(3-nitrobenzyl)phenanthridin-6(5H)-one
-
complete inhibition at 0.01 mM
2,3,8,9-tetrahydroxy-5-(4-nitrobenzyl)phenanthridin-6(5H)-one
-
93% inhibition at 0.01 mM
2,3,8,9-tetrahydroxy-5-[2-(phenylsulfonyl)benzyl]phenanthridin-6(5H)-one
-
95% inhibition at 0.01 mM
2,4-dimethyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-(1,3-benzothiazol-2-yl)-1-(2-chlorobenzyl)-4-methyl-5-(morpholin-4-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(2-methoxyethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(1,3-benzothiazol-2-yl)-4-methyl-1-(pyridin-2-ylmethyl)-5-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(1,3-benzothiazol-2-yl)-4-methyl-5-(morpholin-4-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(1,3-benzothiazol-2-yl)-5-[2-(1H-imidazol-4-yl)ethyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(1,3-benzothiazol-2-yl)-5-[2-(1H-indol-3-yl)ethyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2,5-dichlorobenzyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-(2-chloro-4-fluorobenzyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-(2-chloro-4-fluorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]-pyridine-3,6(2H,5H)-dione
-
-
2-(2-chloro-4-fluorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chloro-4-fluorophenyl)-5-(2-pyridin-2-ylethyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
-
2-(2-chlorophenyl)-4-(2-fluorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-([methyl(phenyl)amino]methyl)-5-[2-(pyridin-2-yl)ethyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-methyl-5-(3-phenylprop-2-yn-1-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-methyl-5-(4-[(4-methylpiperazin-1-yl)methyl]benzyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo-[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-methyl-5-[(6-morpholin-4-ylpyridin-2-yl)-methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-methyl-5-[4-(4-methylpiperazin-1-yl)-4-oxobutyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-[[4-(3-methoxyphenyl)piperazin-1-yl]-methyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-[[methyl(phenyl)amino]methyl]-5-(pyridin-4-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-5-(3-ethoxypropyl)-4-methyl-1-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-5-(3-hydroxypropyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-5-(cyclohexylmethyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-5-[(1-methyl-1H-pyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1H-pyrazolo[4,3-c]-pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-5-[2-(dimethylamino)ethyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-methoxyethyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-6-methoxy-4H-chromen-4-one
-
complete inhibition at 0.01 mM
2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one
-
complete inhibition at 0.01 mM
2-(3,4-dihydroxyphenyl)-5-hydroxy-3,7-dimethoxy-4H-chromen-4-one
-
88% inhibition at 0.01 mM
2-(4-chlorobenzyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-(4H-3,1-benzothiazin-2-yl)-1-benzyl-4-methyl-5-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(7-chloroquinolin-4-yl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-benzyl-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-[(2,3,8,9-tetrahydroxy-6-oxophenanthridin-5(6H)-yl)methyl]benzonitrile
-
97% inhibition at 0.01 mM
2-[(2E)-2-(3,4-dihydroxybenzylidene)hydrazinyl]-N-(3-nitrophenyl)-2-oxoacetamide
-
96% inhibition at 0.01 mM
2-[2-(4-chlorophenoxy)ethyl]-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-[4-(benzyloxy)phenyl]-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
3,5,7-trihydroxy-2-(4-hydroxy-3-methylphenyl)-4H-chromen-4-one
-
94% inhibition at 0.01 mM
3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
-
complete inhibition at 0.01 mM
3-(3,4-dihydroxycyclohexa-2,4-dien-1-yl)-2,7-dihydroxy-4H-chromen-4-one
-
86% inhibition at 0.01 mM
3-(3-chlorophenyl)-N-[2-(piperazin-1-yl)phenyl]-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxamide
-
Shionigi compound
3-(3-chlorophenyl)-N-[4-(piperidin-4-yl)phenyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide
-
-
3-(4,5-dimethyl-3,6-dioxo-1,3,5,6-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)benzonitrile
-
-
4,5-dimethyl-2-(4-phenyl-1,3-thiazol-2-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4,5-dimethyl-2-(5-[(4-methylpiperazin-1-yl)sulfonyl]pyridin-2-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-(2-aminoethyl)benzenesulfonyl fluoride
-
significantly reduces reactive oxygen species production, NADPH oxidase activity, and all the apoptotic events, and cell death induced by both 5 mM KCl and staurosporin
4-methyl-2-(2-methylphenyl)-5-(pyridine-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-methyl-2-phenyl-5-(2-phenylethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]-pyridine-3,6(2H,5H)-dione
-
-
-
4-methyl-3-methylidene-2-(2-phenylethyl)-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
4-methyl-3-methylidene-2-[2-(morpholin-4-yl)ethyl]-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
4-methyl-5-(3-phenoxybenzyl)-2-([1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-[(4-fluorophenoxy)methyl]-5-(2-methoxyethyl)-2-(2-morpholin-4-ylethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(pyrazin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-[[(2-chlorobenzyl)oxy]methyl]-2-(2-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-[[2-(1,3-benzothiazol-2-yl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]methyl]benzoic acid
-
-
4-[[2-(2-chlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]methyl]benzenesulfonamide
-
-
4-[[benzyl(methyl)amino]methyl]-2-(2-chloro-4-fluorophenyl)-5-(3-methoxypropyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
-
complete inhibition at 0.01 mM
5-(1,3-benzodioxol-5-ylmethyl)-4-methyl-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
5-(E)-6,9-deoxa-6,9alpha-methylene-15-cyclopentyl-16,17,18,19,20-pentanor-prostaglandin I2
-
inhibition of sodiumdodecylsulfate-induced activation in cell free extracts, 0.17 mM, 50% inhibition
5-(furan-2-ylmethyl)-4-methyl-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
5-benzyl-2-(4-fluorophenyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4-ylamine
-
i.e. BAY 41-2272, inhibits the induction of the expression of subunits p22phox and gp91phox by 11alpha,9alpha-epoxymethanoprostaglandin F 2alpha. Enhances nitric oxide-induced relaxations in a concentration-dependent manner
5-[(2,5-dihydroxybenzyl)amino]-2-hydroxybenzoic acid
-
82% inhibition at 0.01 mM
aminoethylbenzenesulfonylfluoride
-
treatment blocks the induction of reactive oxygen species production by the dopaminergic toxin MPP+. Co-treatment with inhibitors aminoethylbenzenesulfonylfluoride, apocynin, or diphenylene iodinium significantly suppresses MPP*-induced cell death and attenuates MPP*-induced increases in caspase-3 enzymatic activity
angiotensin
-
angiotensin-(1-7) decreases the elevated levels of renal NADPH oxidase activity and attenuates the activation of subunit NOX-4 gene expression in the diabetic hypertensive kidney. Angiotensin-(1-7) treatment increases sodium excretion but does not affect mean arterial pressure in diabetic hypertensive rats. The significant increase in urinary protein in the diabetic compared to control hypertensive rat is reduced by angiotensin-(1-7). Angiotensin-(1-7) treatment also attenuates the diabetes-induced increase in renal vascular responsiveness to endothelin-1, norepinephrine, and angiotensin II in hypertensive rats, but significantly increases the vasodilation of the renal artery of hypertensive and diabetic hypertensive rats to the vasodilator agonists
betaPix
-
guanine nucleotide exchange factor, overexpression of the central PH domain of betaPix results in inhibition of superoxide anion generation in response to EGF
-
betulinic acid
-
attenuates the expression of NAD(P)H oxidase subunits Nox4 and p22phox, thereby reducing oxidative stress and improving endothelial nitric oxide synthase function. Treated cells show in increased production of bioactive nitric oxide
Cdc42
-
a small monomeric GTPase, competitive inhibitor of Nox2, might also be a competitive inhibitor of Nox1
-
CoA
NADH-dependent oxidase activities is strongly inhibited by addition of free CoA, whereas NADPH dependent activity is not; NADH-dependent oxidase activities is strongly inhibited by addition of free CoA, whereas NADPH dependent activity is not; NADH-dependent oxidase activities is strongly inhibited by addition of free CoA, whereas NADPH dependent activity is not; NADH-dependent oxidase activities is strongly inhibited by addition of free CoA, whereas NADPH dependent activity is not
endothelin-1
-
inhibits NADPH oxidase activity, superoxide generation, and cell proliferation in human abdominal aortic endothelial cells via the ETB1-Pyk2-Rac1-Nox1 pathway. Endothelin-1 significantly attenuates NADPH oxidase activity and cell proliferation, which can be abolished by silencing of the Nox1 gene. RNA interference silencing of ETB1 receptors significantly increases NADPH oxidase activity, and blocks the inhibitory effect of endothelin-1 on NADPH oxidase activity. Endothelin-1 also attenuates angiotensin II-induced activation of NADPH oxidase and cell proliferation
gp91ds
-
fusion peptide that inhibits assembly of NADPH oxidase by mimicking the gp91phox docking site for the cytoplasmic p47phox subunit. gp91ds prevents NADPH oxidase activity, cytokine release, and neurotoxicity induced by HIV regulatory protein Tat in primary microglia
-
Hemin
-
hemin treatment increases hemin oxidase-1 expression and activity in aorta and kidney of apolipoprotein E–deficient mice and significantly reduces both NADPH oxidase activity and superoxide generation in situ
N'1,N'2-bis[(E)-(2,3-dihydroxyphenyl)methylidene]ethanedihydrazide
-
complete inhibition at 0.01 mM
N'1,N'2-bis[(E)-(3,4-dihydroxyphenyl)methylidene]ethanedihydrazide
-
complete inhibition at 0.01 mM
N-(3-aminophenyl)-N'-[1-(4-hydroxy-3-methoxyphenyl)ethyl]ethanediamide
-
complete inhibition at 0.01 mM
N-[(3Z)-3-(4-hydroxy-3-methoxybenzylidene)-2-oxo-2,3-dihydro-1H-indol-5-yl]acetamide
-
complete inhibition at 0.01 mM
N-[1-(3,4-dihydroxyphenyl)ethyl]-N'-(3-nitrophenyl)ethanediamide
-
complete inhibition at 0.01 mM
N-[2-(2-chlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-2-(4-fluorophenoxy)acetamide
-
-
N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2, 5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide
N-[3-(4,5-dimethyl-3,6-dioxo-1,3,5,6-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)phenyl]acetamide
-
-
N4-(3-aminophenyl)[1]benzothieno[3,2-d]pyrimidine-4,8-diamine
-
98% inhibition at 0.01 mM
N4-(4-aminophenyl)[1]benzothieno[3,2-d]pyrimidine-4,8-diamine
-
complete inhibition at 0.01 mM
nitroglycerin
-
in rats treated with nitroglycerin for three days, superoxide production is increased in all aortic layers, while expression of isoforms nox1, nox2 and nox4 is significantly decreased. In vascular smooth muscle cells exposed to nitroglycerin for 6-24 h, NAD(P)H oxidase activity is increased, in spite of nox1 downregulation
O-methyl-epicatechin
-
inhibits endothelial NAD(P)H oxidase activity and prevents superoxide anion formation
-
phallacidin
-
pretreatment of human pulmonary artery endothelial cells before induction of hyperoxia attenuates hyperoxia-induced cortical actin thickening and reactive oxygen species production
procyanidin B2
-
acts both as a superoxide anion scavenger, and inhibitory to NAD(P)H oxidase, with apocynin-like mode of NADPH oxidase inhibition
prostaglandin E1
-
inhibition of sodiumdodecylsulfate-induced activation in cell free extracts, 0.044 mM, 50% inhibition
rosuvastatin
-
rosuvastatin reduces systolic blood pressure in spontaneously hypertensive rats but does not change plasma lipid levels. Rosuvastatin treatment in spontaneously hypertensive rats significantly decreases reactive oxygen species levels, NAD(P)H activity in retinal ganglion cells, and increases retinal plasmalogen content in spontaneously hypertensive rats, but does not modify the electroretinogram response
sepiapterin
-
induction of oxidative stress, p22phox mRNA, endothelial nitric oxide synthase mRNA, and protein by glucose are lowered by concurrent incubation with sepiapterin
sinomenine
-
morphinan analog, inhibits NAD(P)H oxidase cytosolic subunit p47phox translocation to the cell membrane and thus reduces lipopolysaccharide-induced extracellular reactive oxygen species production. Protects neuron-glial cell cultures at both micro- and sub-picomolar concentrations against dopaminergic neuron death, but not protection is seen at nanomolar concentrations
taxol
-
induces concentration-dependent neuronal death with apoptotoic features. Neuronal death is significantly attenuated by anti-apoptotic rugs and by antioxidants such as trolox, ascorbic acid, and tempol. Exposure to taxol increases the expression of NAD(P)H oxidase subunits p45phox and gp91phox and induces translocation of p47phox protein to the membrane in cortical cultures
telmisartan
-
0.01 mM telmisartan decreases NAD(P)H oxidase activity by 32% in MIN-6 cells
tetramethylpyrazine
-
inhibits the induction of NAD(P)H oxidase activity by angiotensin II and the concomitant increase of intracellular reactive oxygen species levels and ERK phosphorylation
(-)-epigallocatechin gallate
-
inhibition of intracellular reactive oxygen species generation, inhibition of translocation of cytosolic subunits into membrane
(-)-epigallocatechin gallate
-
inhibition of intracellular reactive oxygen species generation
apocynin
-
in cells continuously treated with nitric oxide donors, including nitroglycerin, over 2-3 days, basal production of nitrite and nitrate is diminished. The diminished basal nitric oxide levels are mitigated by intermittent treatment allowing an 8-h daily nitrate-free interval during the 2- to 3-day treatment period. Addition of the NAD(P)H oxidase inhibitor apocynin restores the basal levels of nitric oxides that are decreased by continuous nitroglycerin treatment. Apocynin causes significant improvement of increased mRNA and protein levels of endothelial nitric oxide synthase in cells given nitroglycerin continuously over the treatment period. Apocynin also reduces endothelial production of reactive oxygen species after continuous nitroglycerin treatment
apocynin
-
blocks production of superoxide anion in sarcoplasmic reticulum of coronary arterial myocytes
apocynin
-
in sarcoplasmic reticulum vesicles isolated after exercise and tachycardia, apocynin prevents the increase in ryanodine receptor-2 S-glutathionylation, reduced calcium release activity, and completely prevents the protective effects of exercise and tachycardia on infarct size
apocynin
-
enzyme inhibitor, pretreatment of cells completely blocks insulin-stimulated activation of hypoxia-inducible factor 1
apocynin
-
significantly blunts both the generation of reactive oxygen species and induction of apoptosis induced by apigenin
apocynin
-
4-hydroxy-3-methoxyacetophenonesubstituted, a natural molecule structurally related to vanillin, acts on p47phox, requires a peroxidase such as MPO
apocynin
-
paraquat-induced reactive oxygen species production is inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium. Apocynin and diphenylene iodonium also rescue cells from paraquat-induced toxicity. The inhibitors for protein kinase C delta or extracellular signal-regulated kinases ERK1/2 can partially attenuate paraquat-induced reactive oxygen species production and cell death
apocynin
-
treatment significantly decreases angiotensin II-induced endothelin-1 RNA and peptide expression, superoxide production as well as collagen expression
apocynin
-
aortic rings from mice deificient in subunit p47phox are more sensitive to apocynin-induced dilation than wild-type aortic rings. Rho kinase inhibition reduces or prevents the inhibitory effect of apocynin on agonist-induced vasoconstriction and apocynin inhibits the phosphorylation of Rho kinase substrates
apocynin
-
inhibition of NAD(P)H oxidase by apocynin in ischemia-induced mice prevents blood-brain barrier damage in the ischemic hemisphere I after reperfusion
apocynin
-
inhibits NADPH oxidase and induces increased nitric oxide synthesis by eliciting a generation of reactive oxygen species, which in turn causes transcription factor NF-kappaB activation and increased expression of inducible nitric oxides
apocynin
-
selective NADPH oxidase inhibitor, inhibition of NADPH oxidase protects photoreceptors from light-induced degeneration
apocynin
-
when luminal NaCl in kidney is switched from 10 to 80 mM, a situation of initiating maximum tubuloglomerular feedback response, superoxide anion production significantly increases. In the presence of apocynin, superoxide anion production is inhibited by 80%
apocynin
-
after 14 days, local treatment with apocynin via the adventitia, reduces superoxide generation. Apocynin significantly reduces neointima formation and proliferation of cells in both the neointima and adventitia. Nitric oxide-dependent vasorelaxation to acetylcholine, which is normally impaired in collared arteries, is improved, and apocynin suppresses the endothelial expression of intracellular adhesion molecule- and vascular cell adhesion molecule-
apocynin
-
in rabbits with heart failure induced by myocardial infarction, apocynin reduces NADPH oxidase activity, subunit p47phox protein, oxidative stress, myocyte apoptosis, and Bax protein, increases Bcl-2 protein, and ameliorates left ventricular dilatation and dysfunction
apocynin
-
also named acetovanillone, 4'-hydroxy-3'-methoxyacetophenone
apocynin
-
smoking impaires acetylcholine-induced relaxations of carotid arteries, which can be improved by the NAD(P)H oxidase inhibitor apocynin. Vascular mRNA expression of the proinflammatory cytokines IL-1, IL-6, and TNF-alpha and that of inducible nitric oxide synthase is significantly increased by both smoking and cigarette smoke extract exposure, which can be prevented by apocynin, diphenyleneiodinium, or scavenging of H2O2
apocynin
-
blocks up-regulation of epidermal growth factor receptor ligands and Akt activation by transforming growth factor-beta
apocynin
-
prevents inflammation-mediated toxicity to motor neurons induced by lipopolysaccharide
apocynin
-
apocynin does not reduce arterial pressure acutely in spontaneously hpertensive rats when given orally over 1-week intervals or when given i.v. Apocynin potently inhibits granulocyte NADPH oxidase but not vascular NADPH-oxidase dependent oxygen radical formation unless exogenous peroxidase is added to vascular preparations. Apocynin dilates rat intrarenal and coronary arteries independently of pharmacological interventions that reduce vascular superoxide radical abundance and actions
apocynin
-
inhibition of NAD(P)H oxidase in alveolar macrophage by apocynin results in down-regulation of arginase activity and decrease in arginase I mRNA
apocynin
-
apocynin reduces avascularity and apoptosis in the oxygen-induced retinopathy model
apocynin
-
treatment blocks the induction of reactive oxygen species production by the dopaminergic toxin MPP+. Co-treatment with inhibitors aminoethylbenzenesulfonylfluoride, apocynin, or diphenylene iodinium significantly suppresses MPP*-induced cell death and attenuates MPP*-induced increases in caspase-3 enzymatic activity
apocynin
-
significantly attenuates hypoxia/reoxygenation-induced reactive oxygen species formation in porcine coronary artery endothelial cells and suppresses the hypoxia/reoxygenation-induced endothelial spheroid sprouting
bilirubin
-
bilirubin concentration-dependently reduces NADPH oxidase-dependent superoxide production stimulated by phorbol 12-myristate 13-acetate
bilirubin
-
bilirubin concentration-dependently reduces NADPH oxidase-dependent superoxide production stimulated by angiotensin II in vascular smooth muscle cells
diphenylene iodinium
-
inhibition of NAD(P)H oxidase, causes wild-type plants to phenocopy the isoform rdh2/Atrbohc mutant
diphenylene iodinium
-
treatment of NB-4 cells blocks basal generation of reactive oxygen species and arsenic trioxide-induced apoptosis
diphenylene iodinium
-
significant suppression of release of reactive oxygen species in astrocytes caused by calcium ionophores or opsonized zymosan
diphenylene iodinium
-
NaCl-induced increase in total Ca2+ in plasma membrane vesicles is partially abolished by the addition of diphenyleneiodinium
diphenylene iodinium chloride
-
enzyme inhibitor, pretreatment of cells completely blocks insulin-stimulated activation of hypoxia-inducible factor 1
diphenylene iodinium chloride
-
inhibition of enzyme, resulting in inhibitied growth and reactive oxygen species formation in tobacco pollen tube cultures
diphenylene iodinium chloride
-
inhibits NAD(P)H oxidase, effectively inhibits wound healing in potato tuber, and increases susceptibility to microbial infection and decay in 1-month-old tubers
diphenylene iodonium
-
blocks production of superoxide anion in sarcoplasmic reticulum of coronary arterial myocytes
diphenylene iodonium
-
significantly blunts both the generation of reactive oxygen species and induction of apoptosis induced by apigenin
diphenylene iodonium
-
inhibition of NADPH oxidase. In cells deficient for von Hippel-Lindau tumor suppressor gene, presence of diphenyleneiodonium decreases the expression of hypoxia-inducible factor 2alpha
diphenylene iodonium
-
directly inhibits the activity of enzyme component gp91phox/NOX2, the inhibitor targets the FAD binding sequence found in other flavoproteins and is therefore not specific for NOX2
diphenylene iodonium
-
paraquat-induced reactive oxygen species production is inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium. Apocynin and diphenylene iodonium also rescue cells from paraquat-induced toxicity. The inhibitors for protein kinase C delta or extracellular signal-regulated kinases ERK1/2 can partially attenuate paraquat-induced reactive oxygen species production and cell death
diphenylene iodonium
-
significantly inhibits RCC 786-O tumor formation in athymic mice
diphenylene iodonium
-
significantly reduces reactive oxygen species production, NADPH oxidase activity, and all the apoptotic events, and cell death induced by both 5 mM KCl and staurosporin
diphenylene iodonium
-
treatment blocks the induction of reactive oxygen species production by the dopaminergic toxin MPP+. Co-treatment with inhibitors aminoethylbenzenesulfonylfluoride, apocynin, or diphenylene iodinium significantly suppresses MPP*-induced cell death and attenuates MPP*-induced increases in caspase-3 enzymatic activity
diphenyleneiodonium
-
inhibition of NAD(P)H oxidase abolishes depolarisation of the neutrophil plasma membrane by electron current
diphenyleneiodonium
-
treatment significantly decreases angiotensin II-induced endothelin-1 RNA and peptide expression, superoxide production as well as collagen expression
diphenyleneiodonium
-
vascular mRNA expression of the proinflammatory cytokines IL-1, IL-6, and TNF-alpha and that of inducible nitric oxide synthase is significantly increased by both smoking and cigarette smoke extract exposure, which can be prevented by apocynin, diphenyleneiodinium, or scavenging of H2O2
diphenyleneiodonium
-
blocks up-regulation of epidermal growth factor receptor ligands and Akt activation by transforming growth factor-beta
diphenyleneiodonium
-
NAD(P)H oxidase inhibitor, complete inhibition at 0.001 mM
diphenyleneiodonium
-
significantly attenuates hypoxia/reoxygenation-induced reactive oxygen species formation in porcine coronary artery endothelial cells and suppresses the hypoxia/reoxygenation-induced endothelial spheroid sprouting
gp91ds-tat
-
peptidyl inhibitor. Treatment of engineered tissue blocks of a chamber model significantly reduces the level of reactive oxygen species and retards the tissue formation process. Vessels in treated tissues have smaller lumens than control
honokiol
-
submicromolar concentrations of honokiol suppress the increases of NADPH oxidase activity, Rac-1 phosphorylation, p22phox protein expression, and reactive oxygen species production in high glucose-stimulated HUVEC cells. Honokiol also suppresses high glucose-induced cyclooxygenase-2 upregulation and prostaglandin E2 production. Honokiol can reduce increased caspase-3 activity and the subsequent apoptosis and cell death triggered by high glucose medium
N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2, 5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide
-
i.e. FLZ, squamosamide derivative. FLZ inhibits the translocation of the cytosolic subunit p47phox to the membrane and thus inhibits the activation of NAD(P)H oxidase. In vivo, FLZ significantly protects against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced dopaminergic neuronal loss
N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2, 5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide
-
i.e. FLZ, squamosamide derivative, mediates anti-inflammatory and neuroprotective effects in both lipopolysaccharide-and 1-methyl-4-phenylpyridinium-mediated models of Parkinson's disease. FLZ inhibits the translocation of the cytosolic subunit p47phox to the membrane and thus inhibits the activation of NAD(P)H oxidase
neopterin
-
significantly blunts both the generation of reactive oxygen species and induction of apoptosis induced by apigenin
Phenylarsine oxide
-
partial inactivation and desensitization of activity to Ca2+, effect is completely reversed by addition of 2,3-dimercaptopropanol
rosiglitazone
-
activates 5'-AMP-activated protein kinase which, in turn, prevents hyperactivity of NAD(P)H oxidase induced by high glucose, possibly through protein kinase C inhibition. Rosiglitazone protects endothelial cells against glucose-induced oxidative stress with an 5'-AMP-activated protein kinase-dependent and a PPARgamma-independent mechanism
rosiglitazone
-
treatment of animals for 1 week significantly reduces aortic superoxide production and the mRNA expression of enzyme subunits Nox-1, Nox-2, and Nox-4
VAS3947
-
i.e. 3-benzyl-7-(2-oxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine, specific low micromolar NADPH oxidase inhibitor
VAS3947
-
i.e. 3-benzyl-7-(2-oxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine, specific low micromolar NADPH oxidase inhibitor
additional information
-
metronidazole has no measurable inhibitory effect on the NADPH oxidase activity of RdxA
-
additional information
-
unidentified inhibitor found in 3000 g particulate fraction from patients with Grave's disease
-
additional information
-
epicatechin is a superoxide anion scavenger, but not inhibitory to NAD(P)H oxidase. HUVEC cells are able to convert (-)-epicatechin to its inhibitory O-methyl esters. IC50-values of (-)epicatechin and (+)catechin are above 0.1 mM in cell lysates
-
additional information
-
presence of Candida albicans inhibits by contrasting the assembly of the enzyme on dedritic cell's plasma membrane
-
additional information
-
trimer hydroxylated quinone is the major active compound in AOP-1, with strong inhibitory activity against vascular endothelial cell NADPH oxidase with an IC50 of 0.000031 mM at 22°C, pH not specified in the publication
-
additional information
-
Francisella tularensis inhibits NADPH oxidase activity in a cell-free assay; the regulatory factor fevR is essential for NADPH oxidase inhibition, whereas iglI and iglJ, candidate secretion system effectors, and the acid phosphatase acpA are not
-
additional information
-
V204A mutant is a competitive inhibitor of wild-type p67phox
-
additional information
-
knockout of adenosine A2A receptor significantly decreases NADPH-dependent superoxide anion production in mouse hearts compared to age-matched wild-type controls, accompanied by a significant decrease in catalytic subunit Nox2 protein expression, and down-regulation of ERK1/2, p38MAPK, and JNK phosphorylation. In wild-type mice, intraperitoneal injection of the selective adenosine A2A receptor antagonist SCH58261 inhibits phosphorylation of regulatory subunit p47phox, which is accompanied by a down-regulated cardiac reactive oxygen species production, and decreased JNK and ERK1/2 activation
-
additional information
-
K+ depletion increases superoxide levels, phosphorylation of c-Jun, expression of c-Src, and tyrosine phosphorylation of ROMK channel in renal cortex and outer medulla in wild-type mice. Low K+ intake decreases mean product of channel number and open probability of ROMK channels. In mice lacking the NAD(P)H oxidase subunit gp91phox, the effects of low K intake are significantly attenuated
-
additional information
-
treatment of animals by oral administration of isoobtusilactone A for two weeks does not result in significant difference between control animals and treated animals with respect to the body weight gain, the body weight ratio of liver, spleen and kidney, haematological and clinical chemistry parameters
-
additional information
-
trimer hydroxylated quinone is the major active compound in AOP-1, with strong inhibitory activity against vascular endothelial cell NADPH oxidase with an IC50 of 0.000031 mM at 22°C, pH not specified in the publication
-
additional information
-
mGluR5 activation inhibits microglial NADPH oxidase activity
-
additional information
-
inhibition by addition of hexokinase and glucose to remove ATP
-
additional information
-
non-iodinated lipid aldehydes inhibit depending on their chain length, maximum inhibition with dodecanal and tridecanal, no inhibition with octanal
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
11alpha,9alpha-epoxymethanoprostaglandin F 2alpha
-
induces the expression of subunits p22phox and gp91phox
2,4,6-trinitrophenyl-bovine serum albumin
-
induces reactive oxygen species generation, which occurrs immediately. 2,4,6-Trinitrophenyl-bovine serum albumin but not TG causes extracellular release of superoxide anion/hydrogen peroxide, which is blocked by diphenyleneiodonium, apocynin, and wortmannin. When used together, 2,4,6-trinitrophenyl-bovine serum albumin and thapsigargin evoke the release of leukotriene C4, tumor necrosis factor-alpha, and interleukin-13 as well as reactive oxygen species generation synergistically
-
5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b] pyridin-3-yl]-pyrimidin-4-ylamine
-
i.e. BAY 41-2272. THP-1 cells treated with BAY 41-2272 for 48 h significantly increase the superoxide anion release. BAY 41-2272 increases subunit gp91phox gene expression and causes a significant increase in cGMP and cAMP levels
A23187
-
calcium ionophore. HaCaT keratinocytes overexpressing calcium- and arachidonic acid binding proteins S100A8/S100A9 showed enhanced, transient reactive oxygen species generation in response to A23187, as well as nuclear factor kappaB activation and increase in interleukin-8 mRNA levels
apigenin
-
apigenin reduces cell viability, and induces apoptotic cell death in a dose-dependent manner. In addition, it evokes a dose-related elevation of intracellular reactive oxygen species level. Treatment with various inhibitors of the NADPH oxidase significantly blunts both the generation of reactive oxygen species and induction of apoptosis induced by apigenin
arachidonic acid
-
maximal enzyme activity in the presence of 0.25-0.35 mM, inhibition above
betaPix
-
a Rac1 guanine nucleotide exchange factor, appears to be constitutively bound to Nox1 and essential for its activity
-
bovine serum albumin
-
time-dependent increases in NAD(P)H oxidase activity with bovine serum albumin stimulation that is inhibited in a concentration-dependent manner with the HMG-CoA reductase inhibitor rosuvastatin, or with Rac1 inhibitor NSC23766. Following albumin stimulation, Rac1 translocates to plasma membrane for NAD(P)H oxidase activation
-
calyculin
isoform RbohD is directly phosphorylated in vivo. Phophorylation is enhanced in presence of protein phosphatase inhibitor calyculin. Calyculin itself induces reactive oxygen species production and dramatically enhances the ionomycin-induced reactive oxygen species production of isoform RbohD
cytochalasin D
-
enhancement of basal and hyperoxia-induced reactive oxygen species formation
doxorubicin
-
induction of superoxide production by doxorubicin is much higher in hearts of wild-type mice than in subunit gp91phox knock-out mice
glucose
-
oxidative stress and expression of the NADPH oxidase subunit, p22phox, are both increased, superoxide dismutase 1 and 3 expression lowered and endothelial nitric oxide synthase significantly elevated in microvessel endothelial cells treated with 40mM glucose for 72 h compared to low glucose medium. Oxidative stress, p22phox mRNA, endothelial nitric oxide synthase mRNA, and protein are lowered by concurrent incubation with sepiapterin
H2O2
-
Nox5 can be upregulated and activated by minute concentrations of hydrogen peroxide
heat shock protein 90
-
binding of heat shock protein 90 to the C-terminus of Nox5 appears to stabilize the protein and enhance expression and activity
-
HIV regulatory protein Tat
-
NADPH oxidase mediates Tat-induced superoxide release in microglia and macrophages
-
isoobtusilactone A
-
isoobtusilactone A elicits a concentration-dependent growth impediment with IC50 value of 37.5 microM. Treated cells also display transient increase of reactive oxygen species during the earlier stage of the experiment, followed by the disruption of mitochondrial transmembrane potential. The presence of a reactive oxygen species scavenger N-acetyl-L-cysteine and the inhibitor of NADPH oxidase diphenyleneiodonium chloride block reactive oxygen species production and the subsequent apoptotic cell death
latrunculin A
-
enhancement of basal and hyperoxia-induced reactive oxygen species formation
lipopolysaccharide
-
exposure tolipopolysaccharide leads to the demise of motor neurons in a dose- and time-dependent manner, whereas interneurons are impaired relatively mildly. NADPH oxidase is activated upon lipopolysaccharide challenge, and inhibitor apocynin prevents inflammation-mediated toxicity to motor neurons
NaCl
-
salt stress results in activiation of plasma membrane NAD(P)H oxidase. NaCl-induced increase in total Ca2+ is partially abolished by the addition of NAD(P)H oxidase inhibitor diphenyleneiodinium
nitroglycerin
-
in vascular smooth muscle cells exposed to nitroglycerin for 6-24 h, NAD(P)H oxidase activity is increased, in spite of isoform nox1 downregulation
p67phox
-
activation domain of p67phox triggers FAD reduction by Nox2. P40phox appears to increase oxidase activity in cooperation with p47phox not by inducing translocation to the membrane, but by retaining the oxidase at the phagosome
-
paraquat
-
paraquat-induced reactive oxygen species production including superoxide anions in BV-2 cells is accompanied by translocation of the p67phox cytosolic subunit of NADPH oxidase to the membrane. Paraquat-induced reactive oxygen species production is inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium. Apocynin and diphenylene iodonium also rescue cells from paraquat-induced toxicity. The inhibitors for protein kinase C delta or extracellular signal-regulated kinases ERK1/2 can partially attenuate paraquat-induced reactive oxygen species production and cell death
phosphatidylinositol 3-phosphate
-
subunit p40phox phosphatidylinositol 3-phosphate binding PX domain has phosphatidylinositol 3-phosphate-dependent and -independent functions. Translocation of subunit p67phox requires the PX domain but not 3-phosphoinositide binding. Activation of the oxidase by p40phox, however, requires both phosphatidylinositol 3-phosphate binding and an Src homology 3 domain competent to bind to poly-Pro ligands
platelet-derived growth factor
-
increases H2O2 production in NIH-3T3 fibroblasts through NADPH oxidase activation mediated by Gi-protein coupled receptors and c-Src kinase
-
Poldip2
-
reactive oxygen species production is enhanced by the multifunctional Poldip2, which also interacts with p22phox, presumably at the beginning of the cytosolic C-terminus, upstream of the region dispensable for Nox4 activity
-
Rac guanine nucleotide exchange factors
-
activate in conjunction with ATP and nucleoside diphosphate kinase
-
Rac1
-
in addition to cytosolic organizers and activators, Nox1 also requires Rac1 for activity. Rac1 interacts directly with the C-terminus of Nox1, even in the absence of Noxa1. Nox1 is stimulated by constitutively active Rac1 and inhibited by Rac1 knockdown. Rac1 provides a crucial mechanism for activation by agonists, particularly in cells that exclusively express Nox1/Noxo1/Noxal. Rac1 does not activate Nox4 in transfected cells. Rac1 may participate in Nox5 activation
-
salbutamol
-
salbutamol treatment enhances superoxide anion production in asthma patients through nitric oxide-mediated mechanisms. It exerts beneficial antioxidant effects through activation of catalase and attenuation of lipid peroxidation
sphingosine 1-phosphate
-
increases H2O2 production in NIH-3T3 fibroblasts through NADPH oxidase activation mediated by Gi-protein coupled receptors and c-Src kinase
thapsigargin
-
evokes a robust burst of intracellular reactive oxygen specie, which occurrs with a significant lag tim. When used together, 2,4,6-trinitrophenyl-bovine serum albumin and thapsigargin evoke the release of leukotriene C4, tumor necrosis factor-alpha, and interleukin-13 as well as reactive oxygen species generation synergistically
transforming growth factor-beta
-
up-regulates isoform nox4 and increases the levels of Rac1 protein, a known regulator of both isoforms Nox1 and Nox2, in a transforming growth factor-beta receptor I-dependent manner and mediates activation of the nuclear factor-kappaB pathway. The inhibitors diphenyleneiodonium and apocynin, and SB431542, an inhibitor of the transforming growth factor-beta receptor I, block up-regulation of epidermal growth factor receptor ligands and Akt activation
-
tumor necrosis factor
-
treatment of fibroblasts induces the formation of a signaling complex containing TNF-R1-associated death domain protein TRADD, receptor interacting protein RIP1, NAD(P)H oxidase Nox1, and the small GTPase Rac1. Formation of this complex plays a key role in tumor necrosis factor-induced necrotic cell death
-
tumor necrosis factor-alpha
-
treatment of monocytic cells and isolated monocytes results in up-regulation of the NAD(P)H oxidase gene, neutrophil cytosolic factor 2. Treated cells have increased levels of mRNA and up-regulated expression of NADPH oxidase subunits p47phox, p67phox, and gp91phox, as well as increased oxidase activity. Pharmacological inhibitors of NF-kappaB activation block tumor necrosis factor-induced up-regulation, which correlates with a reduction in expression of the corresponding oxidase proteins and decreased superoxide anion production
-
Urea
-
increase of activity by 250% in presence of 1 M urea with no apparent perturbation in enzyme structure. Presence of urea prohibits the closing of the active site thus allowing the substrate to bind
(+)-(S)-2-(6-methoxynaphthalen-2-yl)propanoic acid
-
i.e. naproxen, nonsteroidal anti-inflammatory drug. Treatment increases isoform Nox2 expression in endothelial cells and diminishes production of bioactive nitric oxide. In healthy volunteers, treatment reduces nitroglycerin-induced, nitric oxide-mediated vasodilatation of the brachial artery
(+)-(S)-2-(6-methoxynaphthalen-2-yl)propanoic acid
-
i.e. naproxen, nonsteroidal anti-inflammatory drug. Marked increase in expression of isoforms Nox1, Nox2, Nox4, and p22phox. Up-regulation of NAD(P)H oxidases is associated with increased superoxide content in aorta and heart, which may be prevented by inhibitor apocynin
2-(2-(2,6-dichlorophenylamino)-phenyl)acetic acid
-
i.e. diclofenac, nonsteroidal anti-inflammatory drug. Treatment increases isoform Nox2 expression in endothelial cells and diminishes production of bioactive nitric oxide. In healthy volunteers, treatment reduces nitroglycerin-induced, nitric oxide-mediated vasodilatation of the brachial artery
2-(2-(2,6-dichlorophenylamino)-phenyl)acetic acid
-
i.e. diclofenac, nonsteroidal anti-inflammatory drug. Marked increase in expression of isoforms Nox1, Nox2, Nox4, and p22phox. Up-regulation of NAD(P)H oxidases is associated with increased superoxide content in aorta and heart, which may be prevented by inhibitor apocynin
4-(4-methylsulfonylphenyl)-3-phenyl-5H-furan-2-one
-
i.e. rofecoxib, nonsteroidal anti-inflammatory drug. Treatment increases isoform Nox2 expression in endothelial cells and diminishes production of bioactive nitric oxide. In healthy volunteers, treatment reduces nitroglycerin-induced, nitric oxide-mediated vasodilatation of the brachial artery
4-(4-methylsulfonylphenyl)-3-phenyl-5H-furan-2-one
-
i.e. rofecoxib, nonsteroidal anti-inflammatory drug. Moderate increase in expression of isoforms Nox1, Nox2, Nox4, and p22phox. Up-regulation of NAD(P)H oxidases is associated with increased superoxide content in aorta and heart, which may be prevented by inhibitor apocynin
4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
-
i.e. celecoxib, nonsteroidal anti-inflammatory drug. Treatment increases isoform Nox2 expression in endothelial cells and diminishes production of bioactive nitric oxide. In healthy volunteers, treatment reduces nitroglycerin-induced, nitric oxide-mediated vasodilatation of the brachial artery
4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
-
i.e. celecoxib, nonsteroidal anti-inflammatory drug. Moderate increase in expression of isoforms Nox1, Nox2, Nox4, and p22phox. Up-regulation of NAD(P)H oxidases is associated with increased superoxide content in aorta and heart, which may be prevented by inhibitor apocynin
angiotensin II
-
potent stimulator of NAD(P)H oxidase O2- production in the vasculature
angiotensin II
-
potent stimulator of NAD(P)H oxidase O2- production in the vasculature
angiotensin II
-
potent stimulator of NAD(P)H oxidase O2- production in the vasculature
angiotensin II
-
potent stimulator of NAD(P)H oxidase O2- production in the vasculature
formyl-Met-Leu-Phe
-
stimulation. In addition, heterologous expression of subunit p40phox markedly enhances superoxide production in stimulated cells. Upon stimulation with phorbol 12-myristate 13-acetate or formyl-Met-Leu-Phe, p40phox translocates to plasma membrane in a p67phox- and p47phox-dependent manner
ionomycin
reactive oxygen species production by isoform RbohD is induced in presence of ionomycin. Ionomycin induces calcium influx into the cell, and following Ca2+ binding to the EF-hand motif of RbohD, conformational changes result in activation
N-formyl-L-methionyl-L-leucyl-L-phenylalanine
-
store-operated Ca2+ entry is required at the beginning of NADPH oxidase activation in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine in neutrophil-like HL-60 cells. When extracellular Ca2+ is initially removed, early addition of Ca2+ after stimulation causes a complete restoration of Ca2+ entry and H2O2production. Both Ca2+ entry and H2O2 production are decreased by purported SOCE blockers, 2-aminoethoxydiphenyl borane (2-APB) and SK&F 96365. Ca2+ influx in HL-60 cells relies on different membrane transient receptor potential canonical channels and Orai1 for allowing NADPH oxidase activation
N-formyl-L-methionyl-L-leucyl-L-phenylalanine
-
stimulation. Conditional expression of p21-activated kinase-1 PAK1 dominant-positive mutants enhances, whereas dominant-negative mutants inhibit, NADPH oxidase-mediated superoxide generation stimulated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Both Rac1 and the GTP exchange factor VAV1 are required as upstream signaling proteins, and the effect of p21-activated kinase-1 PAK1 on the respiratory burst is mediated through phosphorylation of subunit p47phox
NOXA1
-
in contrast to its Noxo1 partner, Noxa1 activity appears to be tightly regulated. Noxa1 contains four Rac-binding TPR motifs, a Nox activation domain and an SH3 domain that interacts with the prolinerich region of an organizer subunit, But the p40phox-binding PB1 domain is not well conserved and the SH3 domain in the middle of the molecule is missing. Phosphorylation of Noxa1 by protein kinase A favors binding to 14-3-3 and dissociation from Nox1, whereas other kinases appear to decrease Noxa1 affinity for Rac1 and Nox1. In contrast, phosphorylation of Noxa1 by Src on tyrosine 110 increases Nox1 activity
-
NOXA1
i.e. NOX activator 1 activates, the protein is expressed predominantly in colon elithelium and is thus likely to be a physiologically relevant partner of NOX1
-
NOXO1
-
In contrast to its Noxo1 partner, Noxa1 activity appears to be tightly regulated. Unlike p47phox, because Noxo1 lacks an autoinhibitory domain, it is thought to constitutively bind the cytochrome, but similar to p47phox, Noxo1 facilitates oxidase assembly by binding both an activator subunit and p22phox. The proline-rich region of Noxo1 binds to an SH3 domain of the activator, whereas the tandem SH3 domains of Noxo1 bind to the proline-rich region of p22phox. Noxo1 also binds to the dehydrogenase domain of Nox1. The PX domain of Noxo1 provides an essential affinity for membrane phosphoinositides
-
NOXO1
i.e. NOX organizer 1 activates, the protein is expressed predominantly in colon elithelium and is thus likely to be a physiologically relevant partner of NOX1
-
phorbol 12-myristate 13-acetate
-
upon treatment, plasma membranes from stimulated cells show an increased amount of regulatory protein Rac1, but other components of the NAD(P)H oxidase complex do not change before and after the stimulation. When the constitutively active form of Rac, Q61L or GTP-bound Rac1 is added exogenously to the membrane, superoxied anion producing activity is enhanced up to 1.5-fold above the basal level,but GDP-loaded Rac1 does not affect superoxide generating kinetics
phorbol 12-myristate 13-acetate
-
stimualtion. Treated dendritic cells are are more competent in killing Candida albicans
phorbol 12-myristate 13-acetate
-
stimulation. In addition, heterologous expression of subunit p40phox markedly enhances superoxide production in stimulated cells. Upon stimulation with phorbol 12-myristate 13-acetate or formyl-Met-Leu-Phe, p40phox translocates to plasma membrane in a p67phox- and p47phox-dependent manner
phorbol 12-myristate 13-acetate
-
after transfection with calcium- and arachidonic acid binding proteins S100A8/S100A9 genes, HeLa cells show dramatically increased activation of NAD(P)H oxidase in presence of phorbol 12-myristate 13-acetate
phorbol 12-myristate 13-acetate
-
stimulation. Conditional expression of p21-activated kinase-1 PAK1 dominant-positive mutants enhances, whereas dominant-negative mutants inhibit, NADPH oxidase-mediated superoxide generation stimulated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine
Rac
-
small GTPase Rac plays a positive role in isoform Nox3 activation in the presence of subunit p47phox and either subunits p67phox or Noxa1, whereas Rac fails to upregulate Nox3 activity when p47phox is replaced with Noxo1. Expression of constitutively active Rac1 mutant Q61L enhances not only superoxide production but also membrane translocation of p67phox
-
Rac
-
for the activation of Nox enzymes, cytosolic regulatory components (Rac, p67phox, p47phox, and p40phox) are recruited into the integral membrane protein flavocytochrome b558, consisting of the catalytic subunits gp91phox and p22phox
-
thrombin
-
administration of thrombin to endothelial cells leads to upregulation of enzyme subunit p22phox accompanied by a delayed increase in generation of reactive oxygen species and enhanced proliferation. Existence of a positive feedback mechanism, whereby reactive oxygen species lead to elevated levels of p22phox and thus, sustained generation of reactive oxygen species as is observed in endothelial dysfunction
-
thrombin
-
after addition to cell culture, expression of NADPH oxidase subunits p47phox and p67phox occurs, accompanied by up-regulation in the expression of cytosolic enzyme components Rac 1 and p67phox, and the translocation of cytosolic subunits p47phox and p67phox to the membrane. Thrombin-induced reactive oxygen species production, protein oxidation, and loss of cultured hippocampal neurons are partially attenuated by NADPH oxidase inhibition and/or by several antioxidants
-
TNF-alpha
-
activation of enzyme, resulting in an increase in intracellular H2O2 that stimulates Ca2+ sparks and transient Kca currents, leading to a reduction in global concentration of Ca2+ and vasodilation
-
additional information
-
upregulated by agents activationg cAMP pathway
-
additional information
-
presence of Candida albicans does not activate NADPH oxidase in dendritic cells
-
additional information
-
NADPH oxidase can be activated in a cell-free system by mixing cytosol and plasma membranes isolated from resting neutrophils or macrophages in the presence of Mg2+, GTP and an anionic amphiphile such as arachidonic acid or sodium dodecyl sulfate
-
additional information
-
activation of NADPH oxidase in phagocytes can be induced by a large number of inflammatory stimuli such as opsonized bacteria, opsonized zymosan, bacterial formylated peptides such as formyl-Met-Leu-Phe, C5a and platelet-activating factor, and also by pharmacological agents such as calcium ionophores A23127, ionomycin and PKC activators such as phorbol myristate acetate. In intact cells, NADPH oxidase activation is accompanied by phosphorylation of enzyme components p47phox, p67phox, p40phox, p22phox and gp91phox, along with several protein-protein interactions. In human neutrophils, various protein kinases have been implicated in the activation of NADPH oxidase, among which the PKC and MAP kinase families appear to play a major role
-
additional information
-
agonists appear to stimulate Nox1 in specific locations, thus determining where superoxide is produced: extracellularly by muscarinic agonists and thrombin, in endosomes by IL-1beta and TNF-alpha, both inside and outside cells by angiotensin II. Nox activators comprise p67phox and the structurally similar Noxa1. In colon the cytosolic subunits p47phox and p67phox are not expressed and are replaced by Noxo1 and Noxa1. Besides p47phox, other possible organizers include Tks4 and Tks5, two Src substrates with a PX domain and multiple SH3 domains capable of binding p22phox and Noxa1, but not p67phox. Cdc42 cannot activate Nox1
-
additional information
-
superoxide production is induced by addition of NADPH cytochrome P450 reductase
-
additional information
-
when luminal NaCl in kidney is switched from 10 to 80 mM, a situation of initiating maximum tubuloglomerular feedback response, superoxide anion production significantly increases. In the presence of apocynin, superoxide anion production is inhibited by 80%
-
additional information
-
treatment of animals by oral administration of isoobtusilactone A for two weeks does not result in significant difference between control animals and treated animals with respect to the body weight gain, the body weight ratio of liver, spleen and kidney, haematological and clinical chemistry parameters
-
additional information
-
depolarization of membrane potential of endothelial cells leads to activation of NAD(P)H oxidase and, consequently, superoxide anion production
-
additional information
-
StCDPK4 and StCDPK5 phosphorylate and activate the plasma membrane NADPH oxidase
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.015
NADPH
-
subunit p40phox-depleted cytosol in the absencee of recombinant wild-type p40phox, pH 7.3, 37°C
0.024
NADPH
-
subunit p40phox-depleted cytosol in the presence of recombinant wild-type p40phox, pH 7.3, 37°C
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000301
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundec-3-yn-1-yl]octahydro-2,2'-bifuran-5-yl]dodec-4-yn-1-ol
-
-
0.0000123
(1R)-1-[(2R,2'R,5R,5'R)-5'-[(1R)-1-hydroxyundecyl]octahydro-2,2'-bifuran-5-yl]dodecan-1-ol
-
-
0.0000388
(1R,1'R)-1,1'-((2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyl)-bis-(6-(4-n-butylphenoxy)hex-3-yn-1-ol)
-
-
0.0000196
(1R,1'R)-1,1'-((2R,2'R,5R,5'R)-octahydro-2,2'-bifuran-5,5'-diyl)-bis-(6-(4-n-butylphenoxy)hexan-1-ol)
-
-
0.03
1-(2-chlorobenzyl)-4-methyl-5-[3-(2-oxopyrrolidin-1-yl)propyl]-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.03
1-(4-fluorobenzyl)-5-[2-(1H-indol-3-yl)ethyl]-4-methyl-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.00024
1-acetyl-2-(2-chlorophenyl)-4-methyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000398
1-acetyl-4-methyl-2-(2-methylphenyl)-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000409
1-acetyl-4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000285
1-[(3-methoxyphenyl)acetyl]-4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.002175
2,4,5-trimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000387
2,4-dimethyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.03
2-(1,3-benzothiazol-2-yl)-1-(2-chlorobenzyl)-4-methyl-5-(morpholin-4-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.03
2-(1,3-benzothiazol-2-yl)-4-methyl-1-(pyridin-2-ylmethyl)-5-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.001208
2-(1,3-benzothiazol-2-yl)-4-methyl-5-(morpholin-4-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.004729
2-(1,3-benzothiazol-2-yl)-5-[2-(1H-imidazol-4-yl)ethyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.001845
2-(1,3-benzothiazol-2-yl)-5-[2-(1H-indol-3-yl)ethyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000218
2-(2,5-dichlorobenzyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000342
2-(2-chloro-4-fluorobenzyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000213
2-(2-chloro-4-fluorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]-pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000235
2-(2-chloro-4-fluorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000114
2-(2-chloro-4-fluorophenyl)-5-(2-pyridin-2-ylethyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000215
2-(2-chlorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
-
0.000128
2-(2-chlorophenyl)-4-(2-fluorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000172
2-(2-chlorophenyl)-4-([methyl(phenyl)amino]methyl)-5-[2-(pyridin-2-yl)ethyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000158
2-(2-chlorophenyl)-4-methyl-5-(3-phenylprop-2-yn-1-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000515
2-(2-chlorophenyl)-4-methyl-5-(4-[(4-methylpiperazin-1-yl)methyl]benzyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000165
2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo-[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000236
2-(2-chlorophenyl)-4-methyl-5-[(6-morpholin-4-ylpyridin-2-yl)-methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000428
2-(2-chlorophenyl)-4-methyl-5-[4-(4-methylpiperazin-1-yl)-4-oxobutyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000114
2-(2-chlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000065
2-(2-chlorophenyl)-4-[[4-(3-methoxyphenyl)piperazin-1-yl]-methyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000151
2-(2-chlorophenyl)-4-[[methyl(phenyl)amino]methyl]-5-(pyridin-4-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.03
2-(2-chlorophenyl)-5-(3-ethoxypropyl)-4-methyl-1-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.000565
2-(2-chlorophenyl)-5-(3-hydroxypropyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.00052
2-(2-chlorophenyl)-5-(cyclohexylmethyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000047
2-(2-chlorophenyl)-5-[(1-methyl-1H-pyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1H-pyrazolo[4,3-c]-pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000235
2-(2-chlorophenyl)-5-[2-(dimethylamino)ethyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000308
2-(2-fluorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000313
2-(2-methoxyethyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.00034
2-(3-chlorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000259
2-(4-chlorobenzyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.03
2-(4H-3,1-benzothiazin-2-yl)-1-benzyl-4-methyl-5-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.000458
2-(7-chloroquinolin-4-yl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000463
2-benzyl-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000326
2-[2-(4-chlorophenoxy)ethyl]-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.00306
2-[4-(benzyloxy)phenyl]-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000293
3-(4,5-dimethyl-3,6-dioxo-1,3,5,6-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)benzonitrile
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.001947
4,5-dimethyl-2-(4-phenyl-1,3-thiazol-2-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.001418
4,5-dimethyl-2-(5-[(4-methylpiperazin-1-yl)sulfonyl]pyridin-2-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000173
4-methyl-2-(2-methylphenyl)-5-(pyridine-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.005232
4-methyl-2-phenyl-5-(2-phenylethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000373
4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]-pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
-
0.000334
4-methyl-3-methylidene-2-(2-phenylethyl)-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000445
4-methyl-3-methylidene-2-[2-(morpholin-4-yl)ethyl]-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.03
4-methyl-5-(3-phenoxybenzyl)-2-([1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.000153
4-[(4-fluorophenoxy)methyl]-5-(2-methoxyethyl)-2-(2-morpholin-4-ylethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000095
4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(pyrazin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000082
4-[[(2-chlorobenzyl)oxy]methyl]-2-(2-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.004222
4-[[2-(1,3-benzothiazol-2-yl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]methyl]benzoic acid
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000259
4-[[2-(2-chlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]methyl]benzenesulfonamide
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000165
4-[[benzyl(methyl)amino]methyl]-2-(2-chloro-4-fluorophenyl)-5-(3-methoxypropyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.00544
5-(1,3-benzodioxol-5-ylmethyl)-4-methyl-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.00949
5-(furan-2-ylmethyl)-4-methyl-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000878
5-benzyl-2-(4-fluorophenyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000218
N-[2-(2-chlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-2-(4-fluorophenoxy)acetamide
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000328
N-[3-(4,5-dimethyl-3,6-dioxo-1,3,5,6-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)phenyl]acetamide
-
0.1 M phosphate buffer, pH 7.4, 37°C
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.001
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00113
(3Z)-3-(3,4-dihydroxybenzylidene)-5-nitro-1,3-dihydro-2H-indol-2-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00063
(3Z)-3-[4-hydroxy-3,5-di(propan-2-yl)benzylidene]-1,3-dihydro-2H-indol-2-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00017
2,3,8,9-tetrahydroxy-5-(2-hydroxy-5-nitrobenzyl)phenanthridin-6(5H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00026
2,3,8,9-tetrahydroxy-5-(3-nitrobenzyl)phenanthridin-6(5H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00158
2,3,8,9-tetrahydroxy-5-(4-nitrobenzyl)phenanthridin-6(5H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00158
2,3,8,9-tetrahydroxy-5-[2-(phenylsulfonyl)benzyl]phenanthridin-6(5H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00074
2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-6-methoxy-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00085
2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00102
2-(3,4-dihydroxyphenyl)-5-hydroxy-3,7-dimethoxy-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00096
2-hydroxy-5-[(2-hydroxybenzyl)amino]benzoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00059
2-[(2,3,8,9-tetrahydroxy-6-oxophenanthridin-5(6H)-yl)methyl]benzonitrile
Homo sapiens
-
pH and temperature not specified in the publication
0.00102
2-[(2E)-2-(3,4-dihydroxybenzylidene)hydrazinyl]-N-(3-nitrophenyl)-2-oxoacetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00068
3,5,7-trihydroxy-2-(4-hydroxy-3-methylphenyl)-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0012
3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00079
3-(3,4-dihydroxycyclohexa-2,4-dien-1-yl)-2,7-dihydroxy-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00113
5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00134
5-[(2,5-dihydroxybenzyl)amino]-2-hydroxybenzoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.004
ISNSESGPRGVHFIFNKENF
Homo sapiens
-
pH and temperature not specified in the publication
0.00127
methyl 2-hydroxy-5-[(2-hydroxybenzyl)amino]benzoate
Homo sapiens
-
pH and temperature not specified in the publication
0.00091
N'1,N'2-bis[(E)-(2,3-dihydroxyphenyl)methylidene]ethanedihydrazide
Homo sapiens
-
pH and temperature not specified in the publication
0.00116
N'1,N'2-bis[(E)-(3,4-dihydroxyphenyl)methylidene]ethanedihydrazide
Homo sapiens
-
pH and temperature not specified in the publication
0.0013
N-(3-aminophenyl)-N'-[1-(4-hydroxy-3-methoxyphenyl)ethyl]ethanediamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0014
N-[(3Z)-3-(4-hydroxy-3-methoxybenzylidene)-2-oxo-2,3-dihydro-1H-indol-5-yl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00164
N-[1-(3,4-dihydroxyphenyl)ethyl]-N'-(3-nitrophenyl)ethanediamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00024
N4-(3-aminophenyl)[1]benzothieno[3,2-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00107
N4-(4-aminophenyl)[1]benzothieno[3,2-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00083
quercetin 3-O-alpha-D-glucopyranoside
Homo sapiens
-
pH and temperature not specified in the publication
0.034
VWYYRVYDIPPKFFYTRKLL
Homo sapiens
-
pH and temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.16
purified recombinant enzyme, with NADPH in a coupled reaction with (S)-specific ADH from Rhodococcus erythropolis, pH 7.0, 30°C
0.38
purified recombinant enzyme, with NADH in a coupled reaction with (S)-specific ADH from Rhodococcus erythropolis, pH 7.0, 30°C
additional information
-
voltage-clamp experiments, enzyme activity depends on both membrane potential and concentration of NADPH, the shape of the Ie-V curve is influenced by the concentration of NADPH in the submillimolar range
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
the partially purified ReADH shows a preference for an alkaline pH range for the oxidation of (RS)-1-phenylethanol in a coupled reaction with (S)-specific ADH from Rhodococcus erythropolis, the highest activity occurs at pH 12.0
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
70
assay at; assay at; assay at; assay at; assay at
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
80 - 95
-
80°C: about 45% of maximal activity, 95°C: about 45% of maximal activity
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
isoform Nox4 is expressed at high levels in white and brown preadipocytes. Differentiation into adipocytes results in a decrease in their NOX4 mRNA content. In intact adipose tissue, the majority of NOX4 expressing cells are localized within the preadipocyte containing stromal/vascular fracftion. Alterations in NOX4 expression reflects changes in the ratio of adipocyte/interstitial fractions
-
expression of isoform Nox4 mRNA in glioblastomas of WHO grade IV is significantly higher than other astrocytomas of WHO grades II and III
-
expression of cytosolic subunits of NAD(P)H oxidase p47phox and p67phox is not altered by hypercholesterolemia, however, platelets and leukocytes from high cholesterol-fed mice exhibit elevated generation of reactive oxygen species compared to normal diet mice
-
the cytosolic N-terminal segment, containing 4 calcium binding EF-hands is missing in Nox5S, a short calcium-insensitive variant, which is the dominant isoform in carcinoma cells, and expressed together with the long Nox5L in endothelial cells. Nox5S may be constitutively active or be a competitive inhibitor of calcium-dependent activation when present in the same tetrameric complex as Nox5L
-
predominant expression in the dorsal part of zone VII of the endostyle
-
dorsal root ganglion and sympathetic celiac ganglion. mRNA for the NAD(P)H oxidase subunits NOX1, NOX2, NOX4, p47phox, and p22phox is present in both celiac ganglion and dorsal root ganglion, mRNA for NOX4 is significantly higher in celiac ganglion than in dorsal root ganglion. Catalytic subunit p22phox mRNA and protein expression is greater in celiac ganglion of hypertensive rats but not in dorsal root ganglion. Subunit p47phox mRNA and protein, as well as Rac-1protein, are significantly decreased in hypertensive dorsal root ganglion but not in celiac ganglion. Subunit p47phox is translocated from cytoplasm to membrane in hypertensive celiac ganglion but not in hypertensive dorsal root ganglion
-
primary culture of mixed glia. Incubation of cultures in the presence of fibrillar amyloid beta1-42 induces the assembly and the activation of NADPH oxidase, and triggers the production of superoxide anion-derived reactive oxygen species. Pretreatment of microglia with melatonin dose-dependently prevents the activation of NADPH oxidase and decreases the production of reactive oxygen species. Melatonin inhibits the phosphorylation of the p47phox subunit of NADPH oxidase via a PI3K/Akt-dependent signalling pathway, blocks the translocation of p47phox and p67phox subunit to the membrane, down-regulates the binding of p47phox to gp91phox, and impairs the assembly of NADPH oxidase
-
expression of isoform Nox4 mRNA in glioblastomas of WHO grade IV is significantly higher than other astrocytomas of WHO grades II and III
-
the plant hormone abscisic acid triggers production of reactive oxygen species in guard cells via the AtrbohD and AtrbohF NADPH oxidases, leading to stomatal closure. The ABA-activated SnRK2 protein kinase open stomata 1 (OST1) regulates AtrbohF activity
high expression; high expression; high expression; high expression
-
-
-
infection by the pathogen Phytophthora infestans results in a radical burst mediated by mitogen-activated protein kinase cascades MEK2-SIPK/NTF4 and MEK1-NTF6. Silencing of the NAD(P)H oxidase Respiratory Burst Oxidase Homolog B, RBOHB eliminates generation of reactive oxygen speicies. INF1 elicitin, produced by the pathogen, regulates reactive oxygen species generation through mitogen-activiated protein kinase cascades
Duox1 and Duox2 localize distinctly in lung epithelial cells as well as in ex-vivo differentiated lung epithelia. The localization of functional Duox-DuoxA heterodimers seems to be controlled by the associated DuoxA subunit; Duox1 and Duox2 localize distinctly in lung epithelial cells as well as in ex-vivo differentiated lung epithelia. The localization of functional Duox-DuoxA heterodimers seems to be controlled by the associated DuoxA subunit, including Duox2 expression in ciliated cells in an ex vivo differentiated lung epithelium
NOX2 and NOX4 are the main isoforms present in macula densa cells
-
NADPH oxidase mediates angiotensin II-stimulated protein synthesis downstream of the type 1 receptor AT1 in myometrium smooth muscle cells
-
mesencephalic dopaminergic neuronal cells. Cells express key NAD(P)H oxidase subunits gp91phox and p67phox, and NAD(P)H oxidase are a key determinant of toxin MPP*-mediated dopaminergic degeneration
-
depleting Rac1 (a component of NADPH oxidase) in mouse rod photoreceptors protects them from photo-oxidative stress without affecting their structure or function
-
NAD(P)H oxidase is most abundant in the pons compared to other regions of the brain. Cytoplasmic superoxide dismutase is equally distributed among different regions but catalase and glutathione peroxidase are more abundant in pons, hypothalamus and medulla and less so in the cortex and cerebellum
-
(pro)renin receptor is constitutively expressed in renal glomeruli and tubules. Expression of the receptor is upregulated in diabetes via enhancement of angiotensin subtype 1 receptor-NADPH oxidase activity
-
microinjection of lipopolysaccharide bilaterally into the rostral ventrolateral medulla induces progressive hypotension, bradycardia, and reduction in sympathetic vasomotor outflow. This is accompanied by an increase in superoxide anion production for 60-240 min, alongside phosphorylation of subunits p47phox or p67phox, upregulation of gp91phox or p47phox protein, and increase in Rac-1 or NADPH oxidase activity during 60-120 min, and a depression of mitochondrial respiratory enzyme activity during 120-240 min. Inhibition of NADPH oxidase or knockdown of the gp91phox or p47phox gene blunts the early phase of 60-150 min, coenzyme Q10 or mitochondrial KATP channel inhibitor antagonizes the delayed phase of 120-240 min of lipopolysaccharide-nduced increase in superoxide anion production in rostral ventrolateral medulla and cardiovascular depression
-
neuroblastoma cell, cells differentiated by retinoic acid die after exposure to glycated albumin, a model of advanced glycation end product-modified protein. Undifferentiated cells are resistant to glycated albumin. Differentiated cells pre-treated with NAD(P)K oxidase inhibitor diphenyleneiodinium or with rottlerin, an inhibitor of protein kinase C delta, are able to prevent neuronal death induced by glycated albumin
-
protein is localized to the rostral sperm head, with some labeling in the equatorial and post-acrosomal regions
-
primary tracheobronchial epithelial cell. Study on enzyme isoforms Duox1 and Duox2 mRNA expression after treatment with multiple cytokines. Duox1 expression is increased severalfold by treatment with Th2 cytokines IL-4 and IL-13, and by polyinosine-polycytydilic acid and rhinovirus infection. Duox2 expression is highly induced following treatment with Th1-cytokine IFN-gamma
-
NAD(P)H oxidase activity from 1-month-old tubers increases to a maximum 18-24 after wounding and then decreases to barely detecable levels by 72 h. Wound-induced responses are lost over a 25- to 30-month storage period. The initial burst of superoxide in response to wounding is mediated by isoform Strboh A
additional information
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Exposure of mouse aortic rings to hypoxia/reoxygenation significantly increases vessel outgrowth, whereas pharmacological inhibition of NADPH oxidase or genetic deletion of the NADPH oxidase subunit, p47phox significantly suppresses these changes. Increases in myocardial serine-threonine kinase Akt and ERK1/2 activation and vascular endothelial growth factor expression are markedly blunted in the subunit p47phox-deficient mouse subjected to myocardial ischemia-reperfusion compared with the wild-type mouse
-
hemin treatment increases hemin oxidase-1 expression and activity in aorta and kidney of apolipoprotein E-deficient mice and significantly reduces both NADPH oxidase activity and superoxide generation in situ. Effects are reversed by tin protoporphyrin-IX and are not associated with changes in isoforms Nox2 or Nox4 protein levels. Inhibition of NADPH oxidase activity by hemin in the aorta is mimicked by bilirubin in vitro
-
aortas of transgenic rats harboring the mouse renin transgene exhibit greater NADPH oxidase activity, reactive oxygen species levels, C-reactive protein, tumor necrosis factor-alpha expression, apoptosis, and wall thickness, which are significantly attenuated by in vivo treatment with angiotensin type 1 receptor blockade by valsartan or the superoxide dismutase/catalase mimetic tempol
-
human pulmonary artery endothelial cell, induction of NAD(P)H oxidase by exposure to hyperoxia for 3 h. Pretreatment of cells with the actin-stabilizing agent phallacidin attenuates hyperoxia-induced cortical actin thickening and reactive oxygen species production, whereas cytochalasin D and latrunculin A enhance basal and hyperoxia-induced reactive oxygen species formation. A 3-h hyperoxic exposure enhances the tyrosine phosphorylation of cortactin and interaction between cortactin and subunit p47phox. Transfection of cells with cortactin small interfering RNA or myristoylated cortactin Src homology domain 3 blocking peptide attenuated reactive oxygen species production and the hyperoxia-induced translocation of p47phox to the cell periphery
-
in the mesenteric arteries of streptozotocin-induced diabetic apoE-deficient mice the expression of nox4 and gp91phox, ie. nox2 subunits of NADPH oxidase are enhanced as are endothelial nitric oxide synthase mRNA and protein
-
study on enzyme activity, function, and expression in cerebral and systemic arteries. Superoxide production from enzyme is 10- to 100fold greater in intracranial arteries, basilar and middle cerebral arteries than in aorta, carotid, renal or mesenteric arteries. Isoform Nox4 shows 10fold higher expression in the basilar arteries versus aorta, carotid and mesenteric arteries
-
smoking impaires acetylcholine-induced relaxations of carotid arteries, which can be improved by the NAD(P)H oxidase inhibitor apocynin. Both smoking and in vitro cigarette smoke extract exposure significantly increase vascular superoxide anion production
-
porcine coronary artery endothelial cell, PCAEC. Exposure of cells to hypoxia for 2 h followed by 1 h of reoxygenation significantly increases reactive oxygen species formation. Pretreatment with the NADPH oxidase inhibitors, diphenyleneiodonium and apocynin , significantly attenuates hypoxia/reoxygenation-induced reactive oxygen species formation. Exposure of PCAECs to hypoxia/reoxygenation causes a significant increase in serine-threonine kinase Akt and ERK1/2 activation. Exposure of PCAEC spheroids to hypoxia/reoxygenation significantly increases endothelial spheroid sprouting, whereas pharmacological inhibition of NADPH oxidase or genetic deletion of the NADPH oxidase subunit, p47phox (p47phox/), significantly suppresses these changes
-
primary culture. Proliferation induced by fibrillar beta-amyloid peptide Abeta1-40 is mediated both by microglial release of TNF-alpha and by production of hydrogen peroxide by enzyme
-
involvement of reactive oxygen species from NADPH oxidase in cytokine induction of secretory phospholipase A2-IIA in astrocytes
-
in ischemic cardiomyocytes, Nox2 is upregulated in the cytosol and targeted to the nuclear pore complex
-
the potent anti-inflammatory, cytokine interleukin-10, acts as a down-regulator of the Nox1-based oxidase in the colon, and suggests an important role of ROS derived from Nox1-based oxidase in the initiation of inflammatory responses of the colon
-
Nox1 is most highly expressed in colon epithelium. In colon the cytosolic subunits p47phox and p67phox are not expressed and are replaced by Noxo1 and Noxa1
-
L-carnitine inhibits angiotensin II increased NADPH oxidase activity and intracellular ROS levels in cardiac fibroblasts
-
primary culture. Proliferation induced by fibrillar beta-amyloid peptide Abeta1-40 is mediated both by microglial release of TNF-alpha and by production of hydrogen peroxide by enzyme
-
keratinocyte cell line. Long-term survival mechanisms in niacin deficient cells involve accumulation of reactive oxygen species and increased DNA damage with concomitant increase in expression and activity of NAD(P)H oxidase
-
after myocardial infarction, NAD(P)H oxidase activity is markedly increased in remote left ventricular myocardium of wild-type mice but not in mice deficient in subunit p47phox. Increased myocardial xanthine oxidase activity is observed in wild-type, but not in p47phox-deficient mice after myocardial infarction. Left ventricular cavity dilatation and dysfunction 4 weeks after infarction are markedly attenuated in p47phox-deficient mice and cardiomyocyte hypertrophy, apoptosis, and interstitial fibrosis are substantially reduced as compared with wild-type. The survival rate is markedly higher in mice deficient in subunit p47phox
-
induction of superoxide production by doxorubicin is much higher in hearts of wild-type mice than in subunit gp91phox knock-out mice. Superoxide production is similarly induced by addition of NADPH cytochrome P450 reductase
-
the amount of NOX4 is elevated in hearts of db/db diabetic mice compared to wild-type mice
-
the amount of NOX4 is elevated in hearts of db/db diabetic mice compared to wild-type mice
-
-
rabbits with heart failure induced by myocardial infarction exhibit left ventricular dilatation and systolic dysfunction. Changes are associated with increases in NADPH oxidase activity, subunit p47phox protein expression, 8-hydroxydeoxyguanosine expression, 4-hydroxy-2-nonenal expression, myocyte apoptosis, and Bax protein and a decrease in Bcl-2 protein
-
transfection of isoform Nox3-specific siRNA abrogates H2O2 production and inhibitis exclusively the second phase of p42/44 MAPK phosphorylation and Sp1 DNA binding thus preventing upregulation of VEGF-A mRNA expression
-
taurolithocholylsulfate induces shrinkage in wild-type, but not in subunit p47phox-deficient hepatocytes. Hepatocytes from subunit p47phox knock-out mice are resistant towards taurolithocholylsulfate-induced apoptosis and fail to activate the CD95 system
-
bilirubin concentration-dependently reduces NADPH oxidase-dependent superoxide production stimulated by phorbol 12-myristate 13-acetate
cochlear and vestibular system, NOX3 is highly expressed in specific portions of the inner ear
cochlear and vestibular system, NOX3 is highly expressed in specific portions of the inner ear
high expression; high expression; high expression; high expression
-
hemin treatment increases hemin oxidase-1 expression and activity in aorta and kidney of apolipoprotein E-deficient mice and significantly reduces both NADPH oxidase activity and superoxide generation in situ. Effects are reversed by tin protoporphyrin-IX and are not associated with changes in isoforms Nox2 or Nox4 protein levels
-
salt-sensitive rats consuming a low-salt diet exhibit significant increases in AT 1 receptor, cyclooxygenase-2, plasminogen activator inhibitor PAI and phospho-I kappaB in the kidney as compared to those found in salt-resistant rats. The high-salt diet results in severe hypertension and proteinuria in salt-sensitive but not salt-resistant rats, and marked elevations of renal tissue monocyte chemoattractant protein 1, p22phox, NADPH oxidase subunit 4, angiotensin-II-positive cell count, infiltrating T cells and macrophages and further increases in AT 1 receptor, cyclooxygenase-2, PAI-1 and phospho-IkappaB in the salt-sensitive group
-
(pro)renin receptor is constitutively expressed in renal glomeruli and tubules. Expression of the receptor is upregulated in diabetes via enhancement of angiotensin subtype 1 receptor-NADPH oxidase activity
-
intrarenal infusions of angiotensin II both in vitro and in vivo increase renal vascular resistance, and alpha2-adrenoceptor agonist UK14,304 enhances this response. The interaction between angiotensin II and UK14,304 is blocked by inhibitors of NAD(P)H oxidase
high expression; high expression; high expression; high expression
-
platelets and leukocytes from high cholesterol-fed mice exhibit elevated generation of reactive oxygen species compared to normal diet mice. Hypercholesterolemia-induced leukocyte recruitment is attenuated in Cu,Zn-superoxide dismutase transgenic, and NAD(P)H oxidase-knockout mice on high cholesterol diet. Platelets from NAD(P)H oxidase-knockout mice on high cholesterol diet exhibit low levels of adhesion comparable to those of wild-type on normal diet. Overexpression of Cu,Zn-superoxide dismutase or, to a lesser extent, NAD(P)H oxidase subunit gp91 deficiency restores arteriolar vasorelaxation responses toward normal diet wild-type levels
-
five splice variants of Nox4, named Nox4A through E, are found in lung epithelial cells
-
presence of subunits NOX1, NOXA1, NOXO1, p22phox, p47phox, p40phox, p67phox, NOX2, and NOX4. Hypoxic conditions lead to upregulation exclusively of NOX4 mRNA, concomitant with increased levels in microdissected pulmonary arterial vessels. NOX4 mRNA and protein are localized predominantly in the media of small pulmonary arteries, with increased labeling intensities after chronic exposure to hypoxia. In isolated pulmonary arterial smooth muscle cells, NOX4 is localized primarily to the perinuclear space
-
Burkholderia cenocepacia resides in macrophage vacuoles displaying an altered recruitment of the NADPH oxidase complex at the phagosomal membrane
-
alveolar macrophages. Inhibition of NAD(P)H oxidase by apocynin results in down-regulation of arginase
-
subunit gp91phox gene expression is significantly higher in monocytes from sickle cell disease patients compared with normal controls. Monocytes from patients show higher levels of p47phox phosphorylation compared with normal controls
-
increased superoxide anion generation is present both in endothelial and smooth muscle cells after cigarette smoke extract exposure
-
dorsomedial nucleus tractus solitarius neuron. In small dendritic processes, both angiotensin II and phenylephrine produce a decrease in intracellular subunit p47phox labeling selectively in dorsomedial nucleus tractus solitarius neurons. In intermediate-size dendritic profiles in the dorsomedial nucleus tractus solitarius region only, there is an increase in p47phox labeling in response to each hypertensive agent, although these changes occurre in different subcellular compartments. There is an increase in non-vesicular labeling in response to angiotensin II, but an increase in surface labeling with phenylephrine
-
in primary cultures of cerebellar granule neuron, expression of the components of NADPH oxidase proteins, p40phox, p47phox and p67phox,and p22phox, as well as three homologues of the catalytic subunit, NOX1, 2, and 4
-
hemorrhagic shock/resuscitation activates NAD(P)H oxidase by phosphorylation of subunit p47phox. Activation is significantly diminshed in C3H/HeJ mice, which are not responsive to lipopolysaccharide because of a point mutation of tlr4 affecting the TIR domain. In wild-type, in vitro stimulation of hemorrhagic shock/resuscitation-activated neutrophils with recombinant high-mobility group box HMGB1 causes TLR4-dependent activation of NAD(P)H oxidase as well as increased reactive oxygen species production through both MyD88-IRAK4-p38 MAPK and MyD88-IRAK4-Akt signaling pathways
-
retinal ganglion cell reactive oxygen species and retinal NAD(P)H oxidase activity are higher in spontaneously hypertensive rats than in wild-type rats
-
transcript levels of Nox1 increase in planta and during sclerotial development, transcript levels of Ssnox1 also increase during fungal interaction with plant tissue
-
transcript levels of Nox1 increase in planta and during sclerotial development, transcript levels of Ssnox1 also increase during fungal interaction with plant tissue
-
-
bilirubin concentration-dependently reduces NADPH oxidase-dependent superoxide production stimulated by angiotensin II in vascular smooth muscle cells
high expression; high expression; high expression; high expression
-
protein is localized to the adluminal region of the seminiferous tubules
-
NAD(P)H oxidase may have a role in the structural arrangement and mechanical properties of the airway tissue
-
primary cells. Glucose-mediated decreases in protein kinase G-I levels are inhibited by superoxide scavenger tempol or NAD(P)H oxidase inhibitors diphenylene iodonium or apocynin. High glucose exposure time-dependently increases superoxide production, which is abolished by tempol or apocynin treatment, but not by L-NAME, rotenone, or oxypurinol.Total protein levels and phosphorylated levels of subunit p47phox are increased after high glucose exposure. Transfection of cells with siRNA-p47phox abolishes glucose-induced superoxide production and restores protein kinase G-I protein levels
-
in sarcoplasmic reticulum vesicles isolated after exercise and tachycardia, increase in NAD(P)H oxidase activity, ryanodine receptor-2 S-glutathionylation, and calcium release rates. Cardiac muscle displays significant colocalization of NADPH oxidase and ryanodine receptor-2
additional information
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different tissues screened for ThOX2, except for a weak signal in stomach ThOX2 in exclusively found in thyroid cells
additional information
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different tissues screened for ThOX2, except for a weak signal in trachea ThOX2 in exclusively found in thyroid cells
additional information
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expression of isoform Duox2 in all tissues of the digestive tract examined. Enzyme is located at the apical membrane of the enterocytes in the brush border
additional information
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Nox5 expression is restricted to fewer tissues. Nox4 activity is constitutive, addition of cytosol to membrane fractions in transfected cells does not increase Nox4 activity, also transfection of organizer and activator subunits does not increase reactive oxygen species production
additional information
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chamber model using subcutaneous arteriovenous loop tissue
additional information
-
expression of isoform Duox2 in all tissues of the digestive tract examined. Enzyme is located at the apical membrane of the enterocytes in the brush border
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
; NOX1, Nox1 stimulation in endosomes is dependent on ClC-3, where this ion exchanger is required to balance the electrogenic activity of the enzyme
-
Burkholderia cenocepacia resides in macrophage vacuoles displaying an altered recruitment of the NADPH oxidase complex at the phagosomal membrane
-
after Fcgamma receptor-induced phagocytosis, yellow fluorescent protein-tagged subunits p67phox and p40phox translocate to granulocyte phagosomes before phagosome internalization and accumulation of a probe for phosphoinositol 3-phosphate. p67phox and p47phox accumulation on nascent and internalized phagosomes does not require p40phox or PI3 kinase activity. Translocation of p40phox to nascent phagosomes requires binding to p67phox but not phosphoinositol 3-phosphate
-
-
synaptic and extrasynaptic areas of the plasmalemma, localization of subunit p47phox, in dorsomedial nucleus tractus solitarius neurons of saline-treated animals. Chronic administration of phenylephrine, which produces increases in systolic blood pressure, is associated with a repartitioning of p47phox immunolabeling away from intracellular organelles in distal dendritic areas, and toward the plasma membrane of intermediate dendritic areas of dorsomedial nucleus tractus solitarius neurons
-
-
local production of superoxide anion, which is increased by M1-receptor agonist, oxotremorine and Ca2+ ionophore, A23187, increased. Inhibitors diphenylene iodonium and apocynin, or superoxide dismutase and catalase, and subunit Nox4 siRNA all substantially block this local production of superoxide anion. Sarcoplasmic superoxide anion producing system is controlled by cADPR-RyR/Ca2+ signaling pathway
-
in resting cells, enzyme complex components p22phox and gp91phox are located in the plasma membrane and membranes of specific granules
-
critical role for granules as a site for assembly and activation of the oxidase enzyme system
additional information
-
minor part of protein is expressed at cell surface, not found at surface of transfected CHO and PLB-XCGD cells
-
full-length subunit p40phox exhibits a cytoplasmic localization pattern in resting cells. Upon stimulation with phorbol 12-myristate 13-acetate or formyl-Met-Leu-Phe, p40phox translocates to plasma membrane in a p67phox- and p47phox-dependent manner
-
; NOX components are distributed between the cytosol (p47phox, p67phox, p40phox and Rac1/2) and the plasma membrane and membranes of specific granules
-
in resting cells, enzyme complex components p47phox, p67phox, p40phox and Rac1/2 are localized in the cytosol
-
expression of cytosolic subunits of NAD(P)H oxidase p47phox and p67phox is not altered by hypercholesterolemia
-
subunit p47phox, in dorsomedial nucleus tractus solitarius neurons of saline-treated animals. Administration of angiotensin over 7 days, which produces elevated systemic blood pressure, is associated with a redistribution of p47phox immunolabeling away from intracellular organelles in the distal dendritic compartment, and toward non-vesicular targets in less distal, intermediate areas of dorsomedial nucleus tractus solitarius neurons. Chronic administration of phenylephrine, which produces increases in systolic blood pressure, is associated with a repartitioning of p47phox immunolabeling away from intracellular organelles in distal dendritic areas, andtoward the plasma membrane of intermediate dendritic areas of dorsomedial nucleus tractus solitarius neurons
-
subunit gp91-phox of cytochrome b558 of the multicomponent complex is an integral membrane protein with several membrane-spanning regions
-
the electron current depolarises the neutrophil plasma membrane at a rate of 2.3 V per s and this depolarisation is opposed when voltage-gated proton channels are activated. 3 mM ZnCl2 depolarises the membrane potential to +97.8 mV , and this depolarisation is abolished after NADPH oxidase inhibition
-
active subunit Nox1 endogenously co-localizes with its regulatory components p22phox, NOXO1, NOXA1 and Rac1
-
small GTPase Rac is involved in membrane translocation of subunit p67phox
-
; NOX components are distributed between the cytosol (p47phox, p67phox, p40phox and Rac1/2) and the plasma membrane and membranes of specific granules
-
Nox1, like Nox2, associates with p22phox to form a membrane-bound cytochrome
-
different membrane fractions enriched either in transversal tubules, triads containing transverse tubules attached to sarcoplasmic reticulum vesicles, and junctional sarcoplasmic reticulum vesicles. Enzyme subunits gp91phox, p47phox, p67phox, p22phox are enriched in transversal tubules and triads, but not in sarcoplasmic reticulum
-
exposure to taxol induces translocation of p47phox protein to the membrane in cortical cultures
-
full-length subunit p40phox exhibits a cytoplasmic localization pattern in resting cells. Upon stimulation with phorbol 12-myristate 13-acetate or formyl-Met-Leu-Phe, p40phox translocates to plasma membrane in a p67phox- and p47phox-dependent manner
-
in resting cells, enzyme complex components p22phox and gp91phox are located in the plasma membrane and membranes of specific granules
-
NOX1, NOX5, NOX2, and NOX4. The signal peptide at the N-terminus of Nox1 is important for localization at the plasma membrane, as it is prevented by replacement with the N-terminus of Nox4. A polybasic region in Nox5 with affinity for phosphoinositides may favor translocation to the plasma membrane and extracellular superoxide release
additional information
-
coexpression of enzyme and enzyme maturation factor DuoxA2 allows ER-to-Golgi transition, maturation, and translocation to the plasma membrane of functional isoform Duox2 in a heterologous system
-
additional information
-
in resting cells, enzyme complex components p47phox, p67phox, p40phox and Rac1/2 are localized in the cytosol, whereas p22phox and gp91phox are located in the plasma membrane and membranes of specific granules
-
additional information
-
Nox4 location varies according to cell type, different Nox4 isoforms may be present in specific subcellular locations
-
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
49000
2 * 49000, SDS-PAGE; 4 * 49000, SDS-PAGE
138000
180000
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
homohexamer
6 * 50000, SDS-PAGE
homotetramer
4 * 49000, SDS-PAGE
additional information
?
-
x * 47000-48000, p47-phox, cytosolic component of the multicomponent complex, SDS-PAGE; x * 65000-67000, p67-phox, cytosolic component of the multicomponent complex, SDS-PAGE
dimer
-
1 * 22000-23000 + 1 * 76000-91000, subunits of the membrane component of the enzyme complex, cytochrome b558, SDS-PAGE
homodimer
; 2 * 49000, SDS-PAGE
additional information
-
guanine nucleotide exchange factor betaPix interacts with enzyme with the PH domain of betaPix binding to the FAD-binding region of enzyme. Additionally, NADPH oxidase organizer 1, NoxO1, interacts with enzyme
additional information
-
the alpha-helical loop of isoform Nox2 is probably involved in the correct assembly of the NADPH oxidase complex, permitting cytosolic factor translocation and electron transfer from NADPH to FAD
additional information
-
subunit p22phox co-immunoprecipitates with Hippel-Lindau tumor suppressor in vivo and is target of ubiquitination
additional information
Duox proteins form functional heterodimers with their respective DuoxA subunits, in close analogy to the phagocyte NADPH oxidase. Characterization of novel DuoxA1 isoforms and mispaired Duox-DuoxA complexes reveals that heterodimerization is a prerequisite for reactive oxygen species production. Functional Duox1 and Duox2 localize to the leading edge of migrating cells, augmenting motility and wound healing. DuoxA subunits are responsible for targeting functional oxidases to distinct cellular compartments in lung epithelial cells; Duox proteins form functional heterodimers with their respective DuoxA subunits, in close analogy to the phagocyte NADPH oxidase. Characterization of novel DuoxA1 isoforms and mispaired Duox-DuoxA complexes reveals that heterodimerization is a prerequisite for reactive oxygen species production. Functional Duox1 and Duox2 localize to the leading edge of migrating cells, augmenting motility and wound healing. DuoxA subunits are responsible for targeting functional oxidases to distinct cellular compartments in lung epithelial cells
additional information
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active phagocyte NADPH oxidase is a multicomponent enzyme complex composed of six proteins: p22phox (phox: phagocyte oxidase), gp91phox/NOX2, p47phox, p67phox, p40phox and the small G-protein Rac1 or Rac2, enzyme structure, overview
additional information
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Nox2 structure homology modeling, and structure and activation mechanism of NOX proteins, overview. Nox2 is composed of two main domains of equal sizes with very different properties. The amino-terminal moiety includes six transmembrane alpha-helices I-VI connected by 5 loops A-E. The cytosolic carboxy-terminal moiety of Nox2 constitutes a dehydrogenase domain that includes consensus binding sites for its NADPH substrate and FAD cofactor. NOX2 p40phox is composed of an N-terminal PX domain, a central SH3 domain and a C-terminal PB1 domain. The C-terminal PB1 domain of p40phox interacts with the PB1 domain of p67phox
additional information
-
interaction between cytosolic regulator subunit Rac and the N-terminal extension of the catalytic subunit is ubiquoitous and requires a substantial part of the N-terminus including the two EF-hand motifs. Interaction may be mediated by Ca2+ in a dynamic manner
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
phosphoprotein
additional information
glycoprotein
-
cytochrome b558 subunit gp91-phox of the multicomponent complex is heavily glycosylated
glycoprotein
-
isoform Duox2, partial glycosylation. Post-translational modifications during the maturation process may be implicated in the mechanism of H2O2 formation by favoring intramolecular superoxide dismutation
glycoprotein
-
3 loops of Nox2 are extracellular and include consensus asparagine glycosylation sites. Phosphorylation of p67phox, mediated by PKCdelta, ERK2 and p38 MAPK, increases superoxide production by Nox2
phosphoprotein
isoform RbohD is directly phosphorylated in vivo. Phophorylation is enhanced in presence of protein phosphatase inhibitor calyculin
phosphoprotein
-
phosphorylation of the Arabidopsis AtrbohF NADPH oxidase by SnRK2 protein kinase open stomata 1 (OST1) protein kinase
phosphoprotein
-
subunit p47phox is a substrate for interleukin-1 receptor-associated kinase-4, which phosphorylates p47phox at residues T133, S288, and T356. p47phox is phosphorylated in granulocytes in response to lipopolysaccharide stimulation. Lipopolysaccharide-dependent phosphorylation of p47phox is enhanced by the inhibition of p38 MAP kinase
phosphoprotein
-
in intact cells, NADPH oxidase activation is accompanied by phosphorylation of enzyme components p47phox, p67phox, p40phox, p22phox and gp91phox, along with several protein-protein interactions. P47phox is phosphorylated on multiple sites located in its carboxy-terminal portion, including serines 303-379, which play a central role in NADPH oxidase activation and regulation
phosphoprotein
-
phosphorylation of serine 461 by protein kinase A, serine 282 by ERK1/2 or p38 MAPK, or serine 172 by PKA or PKC, decreases ROS production by Nox1. Phosphorylation of p40phox on serine and threonine by PKC is increased during stimulation, particularly at threonine 154
phosphoprotein
-
adenosine A2A receptor regulates subunit p47phox phosphorylation and cardiac reactive oxygen species production by NADPH oxidase through MAPK signaling
phosphoprotein
-
Conditional expression of p21-activated kinase-1 PAK1 dominant-positive mutants enhances NADPH oxidase-mediated superoxide generation stimulated by formyl-methionyl-leucylphenylalanine. Stimulation by p21-activated kinase-1 PAK1 is mediated through phosphorylation of subunit p47phox
phosphoprotein
-
hemorrhagic shock/resuscitation activates NAD(P)H oxidase by phosphorylation of subunit p47phox
phosphoprotein
-
in neutrophils of mice deficient for myeloid Src family kinases p59/61hck, p58c-fgr, and p53/56lyn, phosphorylation of NAD(P)H oxidase subunit p40phox is absent, indicating a defect in enzyme activation
phosphoprotein
-
residues S82 and S97 in the N-terminus of isoform RBOHB are potential phosphorylation sites. S82 is phosphorylated by pathogen signals, and protein kinases CDPK4 or CDPK5 phosphorylate S82 and S97 in a calcium-dependent manner
phosphoprotein
-
StCDPK4 and StCDPK5 phosphorylate the plasma membrane NADPH oxidase at S82 and S97 leading to its activation, a variable domain of StCDPK5 confers plasma membrane localization and its ability to phosphorylate its substrate, NADPH oxidase
additional information
-
coexpression of enzyme and enzyme maturation factor DuoxA2 allows ER-to-Golgi transition, maturation, and translocation to the plasma membrane of functional isoform Duox2 in a heterologous system
additional information
-
oxidative folding of wild-type protein in the endoplasmic reticulum is the rate-limiting step in the maturation, which is not faciltated by the speific maturation factor DUOXA2. DUOXA2 may allow for rapid exit of folded protein from the endoplasmatic reticulum or enahnced degradation of mutant protein
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Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme crystallizes as dimer, with each monomer consisting of a FAD-binding domain, a NAD(P)H -binding domain and a dimerization domain. Redox-active C42 is in sulfenic acid state Cys-SOH and shows two conformations, either hydrogen bonded to H10 or hydrogen bonded to FAD O2’ atom. The NAD(P)H-binding domains each contain ATP as ligand, being not inhibitory to the enzyme
-
homology modeling of structure using the crystal structure of Lactobacillus sanfranciscensis. In contrast to Lactobacillus sanfranciscensis, the Lactococcus lactis enzyme does not bind ADP, being consistent with its specificity for NADH
-
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
activity in membranes, approx. 50% activity are lost after 1 h, freeze/thawing accelerates inactivation, loss of 90% activity after 1 h
65
the enzyme shows a 25% loss of activity after incubation at 65°C for 1 h
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
association with p22phox is required for Nox4 activity, the 2 proteins stabilize each other
-
CHAPS is the best detergent for solubilization of enzyme, preserves native properties of enzyme
-
Nox1 activity is dependent on chaperones Hsp90 and PDI, which appear to be necessary not only for protein folding after synthesis, but also to maintain enzyme stability
-
resistance to trypsin, cleavage of in two major fragments of about 21 and 14 kDa is obtained after incubation of the protein for 20 h at 37°C in the
-
the enzyme is resistant against chemical and physical denaturating agents
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from Escherichia coli strain BL21-CodonPlus(DE3)-RIL partially by heat treatment at 65°C for 15 min
recombinant His6-tagged wild-type and E99Q/E143Q mutant Ca2+ binding domain of NOX5 from Escherichia coli strain BL21(DE3) by nickel affinity and hydrophobic interaction chromatography, followed by ultrafiltration
-
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning of a fragment of pollen specific tobacco NAD(P)H oxidase closely related to that of Arabidopsis thaliana
-
cloning of full length cDNA
Cos-7, CHO, Hek293, NIH3T3, HeLa and PLB-XCGD cells transfected with ThOX2 DNA, protein is expressed but is exclusively found in cytoplasm and shows no activity
-
enzyme subunits gp91phox, p22phox, p47phox, p67phox, and p40phox. Cloning and comparison of sequence and expression with several fish and mammals; enzyme subunits gp91phox, p22phox, p47phox, p67phox, and p40phox. Cloning and comparison of sequence and expression with several fish and mammals; enzyme subunits gp91phox, p22phox, p47phox, p67phox, and p40phox. Cloning and comparison of sequence and expression with several fish and mammals; enzyme subunits gp91phox, p22phox, p47phox, p67phox, and p40phox. Cloning and comparison of sequence and expression with several fish and mammals
expression in Escherichia coli; expression in Escherichia coli; expression in Escherichia coli; expression in Escherichia coli; expression in Escherichia coli
expression of His6-tagged wild-type and E99Q/E143Q mutant Ca2+ binding domain, residues 1-169, of NOX5 in Escherichia coli strain BL21(DE3)
-
gene nox1, DNA and amino acid sequence determination and analysis, quantitative real-time PCR expression analysis, recombinant expression in wild-type Trichoderma harzianum leading to increased levels of Nox1, which is accompanied by an increase in reactive oxgen species production during their direct confrontation with Pythium ultimum. The transformants display an increased hydrolytic pattern
gene tk0304, functional expression in Escherichia coli strain BL21-CodonPlus(DE3)-RIL
genes Ssnox1 and Ssnox2, semiquantitative RT-PCR expression analysis, recombinant expression o f Nox1 and Nox2 in wild-type Sclerotinia sclerotiorum by protoplast transformation
-
stable transfection of COS-7 cells of subunits gp91phox, p22phox, p67phox, p47phox, and also p40phox fused to the N-terminus of green fluorescent protein
-
StRBOHB, expression in Nicotiana benthamiana leaves via transformation by Agrobacterium GV3101 using electropartion and infiltration
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
2 mM metformin induces suppression of NAD(P)H oxidase activity by 45% in high glucose (30 mM) and by 60% in normal glucose concentrations (5.6 mM)
-
5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-induced suppression of NAD(P)H oxidase subunit expression is AMP-activated protein kinase alpha2-dependent
a strong upregulation of NAD(P)H oxidase subunits p22phox and p47phox is observed in the hypertensive kidney of aortic coarcted rats
-
expression of NOX4 mRNA is significantly higher 12 h and 24 h after transient middle cerebral artery occlusion in the basal ganglia and neocortex of wild type mice than in sham-operated controls
-
high glucose concentration (30 mM) increases NAD(P)H oxidase activity by about 27%
-
interleukin-3 incubation stimulates the synthesis of Nox2 cytosolic sub-unit p47phox
-
ischemia/reperfusion injury stimulates the expression of a 28000 Da NOX4 spliced isoform
-
losartan administration significantly reduces oxidative stress generation by decreasing NAD(P)H oxidase expression
-
loss of AMP-activated protein kinase activity increases NAD(P)H oxidase subunit expression (gp91phox, p47phox, p67phox, NOX1 and -4) and NAD(P)H oxidase-mediated superoxide production
NAD(P)H oxidase activity is increased in hypertension
NAD(P)H oxidase activity is increased in noninfarcted left ventricular tissues from mice in the high fat diet plus myocardial infarction group
-
NAD(P)H oxidase activity is not increased in mice from the normal diet plus myocardial infarction group
-
NADPH oxidase activity in the hippocampal CA1 region is significantly elevated in placebo versus sham control as early as 30 min after reperfusion, with peak NADPH oxidase activity levels observed at 3 h. 17Beta-estradiol attenuates NADPH oxidase activity in hippocampal CA1 after global cerebral ischemia
-
NADPH oxidase activity is significantly increased in both the periventricular region and cortex of pups with intraventricular hemorrhage than glycerol- and saline-treated controls at 6h age, and remains substantially elevated at 24h postnatal age
-
NADPH oxidase expression (p22phox and p47phox) and NADPH oxidase-dependent superoxide anion production are not modified in 12 week high-fat highsucrose diet-fed rats
-
NOX1 is upregulated by angiotensin II, PDGF, PGF, LDL, TNF-alpha, oscillatory shear stress BMP4, aldosterone plus salt, IFN-gamma, ET-1, T3, urokinase8, oxidized LDL, and vascular injury. NOX2 is upregulated by angiotensin II, ET-1, TGF-beta, IFN-gamma, oxidized LDL oscillatory shear stress, aldosterone plus salt, Ischemia, and vascular injury.NOX4 is upregulated by TGF-beta, thromboxane, TNF-alpha. IFN-gamma, urotensin, urokinase, oscillatory shear stress, hypoxia, hyperoxia vascular injury. NOX5 iss upregulated by angiotensin II, ET-1, thromboxane A2, TNF-alpha, atherosclerosis. Nox5 can be upregulated and activated by minute concentrations of hydrogen peroxide. In ischemic cardiomyocytes, Nox2 is upregulated in the cytosol and targeted to the nuclear pore complex
-
NOX4 gene expression is stronger in brain samples from stroke patients compared to healthy controls
-
Nox4 mRNA expression increases to 88% in fibroblasts cultured on 3-deoxyglucosone-collagen for 24 h compared to fibroblasts cultured on native collagen
-
oxidized low-density lipoprotein increases the amounts of NADPH oxidase in fibroblasts. Treatment with physiologically relevant levels of glycated low-density lipoprotein increases superoxide and H2O2 release and the levels of NOX4 and p22phox, an essential component of multiple NOX complexes, in wild-type or HSF1-deficient mouse embryonic fibroblasts. Small interfering RNA for p22phox prevents the increase in expression of Nox4 in fibroblasts. The results suggest that glyLDL increases the abundance of NOX4 or p22phox via an HSF1-independent pathway, but that of PAI-1 via an HSF1-dependent manner
the level of p47phox protein, an NAD(P)H oxidase subunit, is increased by angiotensin II treatment (0.01 mM) with a peak being reached at 8 h. This increase is reduced by 0.001 mM diphenyleneiodonium and 0.001 mM telmisartan treatment
-
transcript levels of Ssnox1 increase during fungal interaction with plant tissue
tumor necrosis factor-alpha activates NADPH oxidase expression/activity. NAD(P)H oxidase is increased in the retina of diabetic rats
-
5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-induced suppression of NAD(P)H oxidase subunit expression is AMP-activated protein kinase alpha2-dependent
-
5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-induced suppression of NAD(P)H oxidase subunit expression is AMP-activated protein kinase alpha2-dependent
-
loss of AMP-activated protein kinase activity increases NAD(P)H oxidase subunit expression (gp91phox, p47phox, p67phox, NOX1 and -4) and NAD(P)H oxidase-mediated superoxide production
-
loss of AMP-activated protein kinase activity increases NAD(P)H oxidase subunit expression (gp91phox, p47phox, p67phox, NOX1 and -4) and NAD(P)H oxidase-mediated superoxide production
-
oxidized low-density lipoprotein increases the amounts of NADPH oxidase in fibroblasts. Treatment with physiologically relevant levels of glycated low-density lipoprotein increases superoxide and H2O2 release and the levels of NOX4 and p22phox, an essential component of multiple NOX complexes, in wild-type or HSF1-deficient mouse embryonic fibroblasts. Small interfering RNA for p22phox prevents the increase in expression of Nox4 in fibroblasts. The results suggest that glyLDL increases the abundance of NOX4 or p22phox via an HSF1-independent pathway, but that of PAI-1 via an HSF1-dependent manner
-
oxidized low-density lipoprotein increases the amounts of NADPH oxidase in fibroblasts. Treatment with physiologically relevant levels of glycated low-density lipoprotein increases superoxide and H2O2 release and the levels of NOX4 and p22phox, an essential component of multiple NOX complexes, in wild-type or HSF1-deficient mouse embryonic fibroblasts. Small interfering RNA for p22phox prevents the increase in expression of Nox4 in fibroblasts. The results suggest that glyLDL increases the abundance of NOX4 or p22phox via an HSF1-independent pathway, but that of PAI-1 via an HSF1-dependent manner
-
-
transcript levels of Ssnox1 increase during fungal interaction with plant tissue
-
transcript levels of Ssnox1 increase during fungal interaction with plant tissue
-
-
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S174A
-
substitution of Ser174 to Ala results in about 40% reduction in the phosphorylation of AtrbohF by SnRK2 protein kinase open stomata 1 (OST1)
D484T
-
mutant of the alpha-helical loop of isoform Nox2, neither NADPH oxidase nor iodonitrotetrazolium reductase activity
D500A
-
mutant of the alpha-helical loop of isoform Nox2, neither NADPH oxidase nor iodonitrotetrazolium reductase activity
D500G
-
mutant of the alpha-helical loop of isoform Nox2, neither NADPH oxidase nor iodonitrotetrazolium reductase activity
D500R
-
mutant of the alpha-helical loop of isoform Nox2, neither NADPH oxidase nor iodonitrotetrazolium reductase activity
D506N
E99Q/E143Q
-
site-directed mutagenesis, mutation in the Ca2+ binding domain of NOX5
K195A
-
mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
K195E
-
mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
medicine
epigenetic silencing of Duox is frequently observed in lung cancer
P437H
-
the mutation in the canonical NADPH binding motif of Nox4, analogous to the Nox2 mutation of a CGD patient, abolishes activity
Q36H
-
naturally occuring missense mutation. Mutation completely prevents routing of the protein to the cell surface. Protein is predominantly present as core N-glycosylated, thiol-reduced folding intermediate and retained within the endoplasmic reticulum
R198A/R198A
-
mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
R198Q/R199Q
-
mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
R199E
-
mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
R199Q
-
mutation in D-loop of isoform Nox2. Formylmethionine-activated mutant shows 4- to 8fold higher activity than wild-type
R376W
-
naturally occuring missense mutation. Mutation completely prevents routing of the protein to the cell surface. Protein is predominantly present as core N-glycosylated, thiol-reduced folding intermediate and retained within the endoplasmic reticulum
R57Q
-
mutation in the phophatidylinositol 3-phosphate binding region of subunit p47phox. Mutation abrogates phophatidylinositol 3-phosphate binding and produces a dominant inhibitory effect on agonist-induced superoxide production and membrane translocation of subunits p47phox and p67phox. Mutant p40phox displayes increased association with actin and moesin and is found enriched in the Triton X-100-insoluble fraction along with p67phox and p47phox
R57Q/D289A
-
double mutant of subunit p40phox. Mutant fails to associate with subunits p67phox or p47phox in co-immunoprecipitation and Western blotting assays and abolishes the dominant inhibitory effect of mutant R57Q in phorbol 12-myristate 13-acetate- or formyl-Met-Leu-Phe-induced superoxide production
R96E
-
Nox4 is inhibited by an R96E mutation in the cytosolic B loop, a region of the amino-terminal domain that interacts with the NADPH binding site
S303D/S304D/S320D
-
mutant in subunit p47phox,which mimics phosphorylation by p21-activated kinase-1 PAK1. Expression of mutant induces basal superoxide generation in vivo
V674G
-
spontaneous mutation in exon 16 of the Duox2 gene. Thyroid glands of mutant mice are goitrous and contain few normal follicles, anterior pituitaries are dysplastic. Serum thyroxine in homozygotes is about one-tenth the level of controls. The weight of adult mutant mice is approximately half that of littermate controls, and serum IGF-I is reduced. The cochleae of mutant mice exhibit abnormalities characteristic of hypothyroidism, including a delayed formation of the inner sulcus and tunnel of Corti and an abnormally thickened tectorial membrane. Hearing thresholds of adult mutant mice are on average 50-60 decibels above those of controls
medicine
-
mRNA for the NAD(P)H oxidase subunits NOX1, NOX2, NOX4, p47phox, and p22phox is present in both celiac ganglion and dorsal root ganglion, mRNA for NOX4 is significantly higher in celiac ganglion than in dorsal root ganglion. Catalytic subunit p22phox mRNA and protein expression is greater in celiac ganglion of hypertensive rats but not in dorsal root ganglion. Subunit p47phox mRNA and protein, as well as Rac-1protein, are significantly decreased in hypertensive dorsal root ganglion but not in celiac ganglion. Subunit p47phox is translocated from cytoplasm to membrane in hypertensive celiac ganglion but not in hypertensive dorsal root ganglion
S82A/S97A
additional information
D506N
-
heterozygous mutation isolating in clinically unaffected mother and in a brother, while the patient suffering congenital hypothyroidism additionally carries heterozygous mutation ins602g to fsX300
D506N
-
naturally occuring missense mutation. Mutant display a partial deficiency phenotype with reduced surface expression of protein with normal intrinsic activity in generating H2O2. N-glycan moieties of the mutant protein are not subject to normal modification in the Golgi apparatus
S82A/S97A
-
loss of catalytic activity, with concomitant loss of the potential phosphorylation sites
S82A/S97A
-
site-directed mutagenesis, the mutant enzyme is not phosphorylated by StCDPK4 and StCDPK5
additional information
-
mutants lacking the activity of isoform rdh2/Atrbohc exhibit an impaired root epidermal cell wall, and mutant root hair bulges burst more than wild-type when challegned in situ with hypo-osmotic low ionic strength medium
additional information
-
identification of heterozygous mutation in enzyme gene leading to premature stop at codon 300 and resulting in primary hypothyroidism
additional information
-
replacement of D-loop of isoform Nox2 with the homolog of Nox1, Nox3, or Nox4 is fully functional. Formylmethionine-activated mutant D-loopNox4 in Nox2 shows 4- to 8fold higher activity than wild-type
additional information
-
inhibition of subunit Nox4 expression by small interfering RNA reduces angiogenic responses, in both human microvascular and umbilical vein endothelial cells. Overexpression of wild-type Nox4 enhances, whereas expression of a dominant negative form of Nox4 suppresses the angiogenic responses in endothelial cells. These effects are mimicked by exogenous H2O2 and the antioxidant compound ebselen, respectively. Overexpression of Nox4 enhances receptor tyrosine kinase phosphorylation and the activation of extracellular signal-regulated kinase. Nox4 expression also promotes proliferation and migration of endothelial cells, and reduces serum deprivation-induced apoptosis
additional information
-
in cells with knock-out of beta sub-unit of cytochrome b558 of subunit NOX2, a nitric oxide synthase is able to provide NAD(P)H oxidase activity. Mutants produce roughly the same amount of superoxide anion as wild-type cells, but only half the amount of nitric oxide. In presence of nitric oxides synthase inhibitor L-NAME, production of H2O2 and ONOO- by mutant cells is almost abolished
additional information
-
a fusion protein NOXA1N-RacQ61L between truncated subunit NOXA1 residues1-211 and constitutively active Rac1 mutant Q61L exhibits 6-fold increase of the basal Nox1 activity, but C-terminal truncated NOXO1 residues 1-292 show little effect on the activity
additional information
-
the linker region between the phox homology domain and N-terminal SH3 domain plays a role in blocking the binding of the phosphoinositide 3,4-bisphosphate. Replacement of linker residues 151-158 with glycine alters NMR-measured spin lattice relaxation rates and sedimentation velocity, suggesting that the phox homology domain is released from its autoinhibited conformation. The mutant displays phosphoinositide 3,4-bisphosphate binding activity comparable to that of the isolated phox homology domain but has greatly reduced NAD(P)H oxidase activity upon activation
additional information
-
single nucleotide polymorphisms 242C/T and 640A/G in the gene encoding p22phox subunit of NAD(P)H oxidase are marginally significantly associated with asthma, but single nucleotide polymorphisms 640A/G shows a significant association with sensitization to two allergens tested. Haplotype 930G/242T/640A is associated with an increased risk of asthma
additional information
-
knock-down of isoform Nox4 expression by RNAi results in cell-growth inhibition and enhances induction of apoptosis by chemotherapeutic agents in cultured glioma cell lines
additional information
-
knockdown of isoform NOX5-S or NF-kappaB1 p50 by their small interfering RNA significantly inhibits acid-induced cyclooxygenase COX2 expression and prostaglandin PGE2 production in SEG-1 cells. In a Barrett's cell line overexpressing isoform NOX5-S, inhibitor of kappaB is significantly reduced, and luciferase activity increased when these Barrett' s cells are transfected with a plasmid carrying NF-kappaB fused to luciferase. Overexpression of NOX5-S in Barrett’s cells significantly increases H2O2 production,cyclooxygenase COX2 expression, PGE2 production, and thymidine incorporation
additional information
-
silencing of subunit p47phox with siRNA. Active NAD(P)H oxidase is required for vascular endothelial growth factor activation of phosphoinositide 3-kinase-Akt-forkhead, and p38 mitogen-activated kinase, but not extracellular signal-related kinase 1/2 or c-Jnu N-terminal kinase. The permissive role of NADPH oxidase on phosphoinositide 3-kinase-Akt-forkhead signaling is mediated at post-vascular endothelial growth factor receptor levels and involves the nonreceptor tyrosine kinase Src
additional information
-
in cells deficient for von Hippel-Lindau tumor suppressor gene, protein levels of subunit p22phox, of isoform Nox4 and NADPH-dependent superoxide levels are increased. Down-regulation of isoforms Nox1, Nox4, and p22phox expression by small interfering RNA decreases hypoxia-inducible factor 2alpha# protein expression and inhibits Akt and 4E-BP1 phosphorylation
additional information
-
depletion of endogenous subunit p40phoxusing lentiviral short hairpin RNA reduces reactive oxygen species production and impairs bacterial killing by phagolysosomes under conditions where subunit p67phox levels remain constant. Depletion of p40phox reduces both the maximal rate and total amount of ROS produced without altering theKM value of the oxidase forNADPH
additional information
-
Nox5 is unaffected by expression or knockdown p22phox intransfected cells. The cytosolic N-terminal segment, containing 4 calcium binding EF-hands is missing in Nox5S, a short calcium-insensitive variant, which is the dominant isoform in carcinoma cells, and expressed together with the long Nox5L in endothelial cells. Replacing the first transmembrane domain of Nox4 by that of Nox1, or altering the last extracellular loop of Nox4, makes it produce superoxide, rather than peroxide. Deletion of the NADPH binding domain produces a dominant-negative Nox4. Nox1-Nox4 and Nox2-Nox4 chimeras are active without transfection of cytosolic subunits, whereas the opposite Nox4-Nox2 chimera requires activation. Mutation of the proline-rich domain of p22phox required for docking organizers does not affect Nox4 activity
additional information
-
both genes coding for NAD(P)H oxidases, Nox1 and Nox2, are independently required for pathogenicity. Mutants lacking either nox1 or nox2 are incapable of causing plant disease because of unability to bring about appresorium-mediated cuticle penetration. A nox1nox2 double mutant shows significant increase in superoxide production at the hyphal tips
additional information
-
genetic deletion of the NADPH oxidase subunit, p47phox, significantly suppresses increased vessel outgrowth induced by hypoxia/reoxygenation. Increases in myocardial serine-threonine kinase Akt and ERK1/2 activation and vascular endothelial growth factor expression are markedly blunted in the subunit p47phox-deficient mouse subjected to myocardial ischemia-reperfusion compared with the wild-type mouse
additional information
-
high-cholesterol fed mice genetically deficient in NAD(P)H oxidase subunit Nox-2 show an attenuation in impaired endothelium-dependent vasodilation and enhanced superoxide generation compaired to wild-type
additional information
-
mice deficient in NADPH oxidase subunit gp91phox, CYBB mice, are irradiated and receive wild-type hematopoietic cells to generate chimeric CYBB mice. In response to ovalbumin challenge, the chimeric CYBB mice have increased numbers of eosinophils bound to the endothelium as well as reduced eosinophilia in the lung tissue and bronchoalveolar lavage. Ovalbumin-challenged chimeric CYBB mice have reduced airway hyperresponsiveness that can be restored by bypassing the endothelium with intratracheal administration of eosinophils
additional information
-
mice deficient in NAD(P)H oxidase p47phox show an increase of 17% of the area occupied by airway smooth muscle cells in trachea, compared with wild-type. They exhibit a significantly reduced airway smooth muscle cell relaxation during electric field stimulation and after the end of stimulation
additional information
-
macrophages derived from NADPH oxidase deficient mice display reduced superoxide production, released lower levels of cytokines/chemokines, and induce less neurotoxicity in response to HIV regulatory protein Tat compared to wild-type macrophages
additional information
-
neither mice lacking subunit gp91, lacking myeloperoxidase, nor lymphocyte-deficient recombinase activating gene-1 ko mice develop spontaneous infections when raised under specific pathogen-free conditions and all mice have life spans similar to wild-type animals. Subunit gp91/recombinase activating gene-1 double-deficient but not myeloperoxidase/recombinase activating gene-1 double-deficient mice develop spontaneous multi-organ bacterial and fungal infections early in life and live only a few months. Infections in the gp91/recombinase activating gene-1 double-deficient mice are characterized by granulomatous inflammation of the skin, liver, heart, brain, kidney, and lung. Oyster glycogen-elicited polymorphonuclear neutrophils and macrophages obtained from gp91 ko and gp91/recombinase activating gene-1 double-deficient mice have no detectable NADPH oxidase activity whereas wild-type, recombinase activating gene-1 ko, and myeloperoxidase/recombinase activating gene-1 polymorphonuclear neutrophils and macrophages produce large and similar amounts of superoxide in response to phorbol myristate acetate
additional information
-
compared to wild-type mice with myocardial infarction, subunit gp91phox knockout mice do not display significant difference in infarct size/thickness, cardiac hypertrophy, myocyte apoptosis, inflammatory/fibrogenic responses, as well as cardiac oxidative stress
additional information
-
deletion of subunit gp91phox attenuates angiotensin II-induced responses
additional information
-
aortic rings from mice deificient in subunit p47phox are more sensitive to apocynin-induced dilation than wild-type aortic rings
additional information
-
in mice lacking the subunit gp91phox, the effects of low K intake on superoxide production, c-Jun phosphorylation, c-Src expression, and tyrosine phosphorylation of ROMK channels are significantly attenuated
additional information
-
NOX2-deficient mice serve as chronic granulomatous disease mouse model
additional information
-
in mice deficient in subunit gp91phox, middle cerebral artery occlusion-induced blood-brain barrier disruption and lesion volume in ischemia-induced animals are largely attenuated
additional information
-
mice lacking the NAD(P)H oxidase gp91phox subunit respond to exposure to single-walled carbon nanotubes with a marked accumulation of polymorphnuclear neutrophils and elevated levels of apoptotic cells in the lungs, production of pro-inflammatory cytokines, decreased production of the anti-inflammatory and pro-fibrotic cytokine, TGF-beta, and significantly lower levels of collagen deposition
additional information
-
in obese, diabetic, leptin-receptor deficient db-/db- mice, mRNA levels of enzyme subunits Nox-1, Nox-2, and Nox-4 as well as Nox-2 protein expression are elevated, whereas aortic Cu/Zn superoxide dismutase protein and PPARgamma mRNA levels are reduced
additional information
-
a C242T mutation in the p22phox gene is associated with insulin resistance in non-diabetic subjects
additional information
-
isoform NOX-1 elimination by gene replacement results in complete female sterility, decreased asexual development, and reduction of hyphal growth. The lack of isoform NOX-2 does not affect any of these processes but leads instead to the production of sexual spores that fail to germinate, even in the presence of exogenous oxidants. The elimination of NOR-1, an ortholog of the mammalian Nox2 regulatory subunit gp67phox, also causes female sterility, the production of unviable sexual spores, and a decrease in asexual development and hyphal growth
additional information
-
transfection of tobacco pollen tubes with NAD(P)H oxidase-specific antisense oligodeoxynucleotides results in decreased amount of enzyme mRNA, lower enzyme activity, and tube growth inhibition
additional information
-
transient co-expression of rice cytosolic regulator subunit Rac and the catalytic subunit Rboh enhances production of reactive oxygen species in Nicotiana benthamiana
additional information
-
silencing of genes Ssnox1 and Ssnox2 by siRNA using two silencing vectors (pSNOX1 and pSNOX2) carrying the hygromycin B resistance gene as the selectable marker, defect in sclerotial development of Nox silenced strains, phenotype overview
additional information
-
silencing of genes Ssnox1 and Ssnox2 by siRNA using two silencing vectors (pSNOX1 and pSNOX2) carrying the hygromycin B resistance gene as the selectable marker, defect in sclerotial development of Nox silenced strains, phenotype overview
-
additional information
-
heterologous expression of protein kinase CDPK5 and the catalytic subunit RBOHB in Nicotiana benthamiana results in phosphorylated S82 of RBOHB
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
agriculture
industry
-
mice lacking the NAD(P)H oxidase gp91phox subunit respond to exposure to single-walled carbon nanotubes with a marked accumulation of polymorphnuclear neutrophils and elevated levels of apoptotic cells in the lungs, production of pro-inflammatory cytokines, decreased production of the anti-inflammatory and pro-fibrotic cytokine, TGF-beta, and significantly lower levels of collagen deposition
medicine
synthesis
usage of the enzyme for regeneration of both NADP+ and NAD+ in alcohol dehydrogenase-catalyzed enantioselective oxidation of racemic 1-phenylethanol. NADP+ regeneration at 30°C by TkNOX coupled with (R)-specific ADH from Lactobacillus kefir results in successful acquisition of optically pure (S)-1-phenylethanol, or at 45-60°C with moderately thermostable (S)-specific ADH from Rhodococcus erythropolis in optically pure (R)-1-phenylethanol, giving the possibility to operate the enantioselective bioconversion accompanying NAD+ regeneration at high temperatures, advantage of the combination of thermostable enzymes
additional information
-
NADPH oxidase but not myeloperoxidase is required for host defense in lymphopenic mice. Lymphocytes and NADPH oxidase may compensate for each other's deficiency in providing resistance to spontaneous bacterial infections
agriculture
-
infection by the pathogen Phytophthora infestans results in a radical burst mediated by mitogen-activated protein kinase cascades MEK2-SIPK/NTF4 and MEK1-NTF6. Silencing of the NAD(P)H oxidase Respiratory Burst Oxidase Homolog B, RBOHB eliminates generation of reactive oxygen speicies. INF1 elicitin, produced by the pathogen, regulates reactive oxygen species generation through mitogen-activiated protein kinase cascades
agriculture
-
both genes coding for NAD(P)H oxidases, Nox1 and Nox2, are independently required for pathogenicity of Magnaporthe grisea. Mutants lacking either nox1 or nox2 are incapable of causing plant disease because of unability to bring about appresorium-mediated cuticle penetration
medicine
-
TNF-alpha activates enzyme, resulting in an increase in intracellular H2O2 that stimulates Ca2+ sparks and transient Kca currents, leading to a reduction in global concentration of Ca2+ and vasodilation
medicine
-
mutations in enzyme gene should be considered as the molecular cause of congenital hypothyroidism in young patients with thyroid dyshormogenesis
medicine
-
administration of thrombin to endothelial cells leads to upregulation of enzyme subunit p22phox accompanied by a delayed increase in generation of reactive oxygen species and enhanced proliferation. Existence of a positive feedback mechanism, whereby reactive oxygen species lead to elevated levels of p22phox and thus, sustained generation of reactive oxygen species as is observed in endothelial dysfunction
medicine
-
proliferation of microglial cells induced by fibrillar beta-amyloid peptide Abeta1-40 is mediated both by microglial release of TNF-alpha and by production of hydrogen peroxide by enzyme. TNF-alpha and enzyme, and its products, are potential targets to prevent Abeta-induced inflammatory neurodegeneration
medicine
-
monocytes from sickle cell disease patients show higher levels of NAD(P)H oxidase subunit gp91phox gene expression and p47phox phosphorylation, along with increased interferon-gamma release by lymphocytes
medicine
-
salt sensitivity in the salt-sensitive rat is associated with upregulations of the intrarenal angiotensin system, reactive oxygen species-generating and proinflammatory/profibrotic proteins and an inability to raise antioxidant enzymes and maximally suppress plasma renin activity in response to high salt intake
medicine
-
angiotensin-(1-7) decreases the elevated levels of renal NADPH oxidase activity and attenuates the activation of subunit NOX-4 gene expression in the diabetic hypertensive kidney. Angiotensin-(1-7) treatment increases sodium excretion but does not affect mean arterial pressure in diabetic hypertensive rats. The significant increase in urinary protein in the diabetic compared to control hypertensive rat is reduced by angiotensin-(1-). Angiotensin-(1-7) treatment also attenuates the diabetes-induced increase in renal vascular responsiveness to endothelin-1, norepinephrine, and angiotensin II in hypertensive rats, but significantly increases the vasodilation of the renal artery of hypertensive and diabetic hypertensive rats to the vasodilator agonists
medicine
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water-soluble components of cigarette smoke activate the vascular NAD(P)H oxidase. NAD(P)H oxidase-derived H2O2 activates NF-kappaB, leading to proinflammatory alterations in vascular phenotype, which likely promotes development of atherosclerosis
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increases in myocardial serine-threonine kinase Akt and ERK1/2 activation and vascular endothelial growth factor expression are markedly blunted in the subunit p47phox-deficient mouse subjected to myocardial ischemia-reperfusion compared with the wild-type mouse
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exposure of porcine coronary artery endothelial cells, PCAECs, to hypoxia for 2 h followed by 1 h of reoxygenation significantly increases reactive oxygen species formation. Pretreatment with the NADPH oxidase inhibitors, diphenyleneiodonium and apocynin, significantly attenuates hypoxia/reoxygenation-induced reactive oxygen species formation. Exposure of PCAECs to hypoxia/reoxygenation causes a significant increase in serine-threonine kinase Akt and ERK1/2 activation. Exposure of PCAEC spheroids to hypoxia/reoxygenation significantly increases endothelial spheroid sprouting and vessel outgrowth, whereas pharmacological inhibition of NADPH oxidase or genetic deletion of the NADPH oxidase subunit p47phox significantly suppresses these changes
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in cells continuously treated with nitric oxide donors, including nitroglycerin, over 2-3 days, basal production of nitrite and nitrate is diminished. The diminished basal nitric oxide levels are mitigated by intermittent treatment allowing an 8-h daily nitrate-free interval during the 2- to 3-day treatment period. Addition of the NAD(P)H oxidase inhibitor apocynin restores the basal levels of nitric oxides that are decreased by continuous nitroglycerin treatment. Apocynin causes significant improvement of increased mRNA and protein levels of endothelial nitric oxide synthase in cells given nitroglycerin continuously over the treatment period. Apocynin also reduces endothelial production of reactive oxygen species after continuous nitroglycerin treatment
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wild-type mice fed with high-cholesterol diet exhibit impaired endothelium-dependent vasodilation, enhanced superoxide generation, and increased expression of NAD(P)H oxidase subunit Nox-2 mRNA. In severe combined immunodeficient mice, in mice genetically deficient for interferon IFN-gamma, and CD4+ T-lymphocyte-deficient mice, the impaired endothelium-dependent vasodilation and enhanced superoxide generation are significantly blunted. Effects are similar in high-cholesterol fed mice genetically deficient in NAD(P)H oxidase subunit Nox-2
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vascular cell adhesion molecule-1 induction of NADPH oxidase in the endothelium is necessary for the eosinophil recruitment during allergic inflammation
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mice deficient in NAD(P)H oxidase p47phox show an increase of 17% of the area occupied by airway smooth muscle cells in trachea, compared with wild-type. They exhibit a significantly reduced airway smooth muscle cell relaxation during electric field stimulation and after the end of stimulation. NAD(P)H oxidase may have a role in the structural arrangement and mechanical properties of the airway tissue
medicine
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intravitreal injections of angiotensin II can result in retinal leukostasis, which appears to be mediated via increasing superoxide generation by NAD(P)H oxidase, and by vasular endothelial growth factor. The activity of NAD(P)H oxidase is required for leukostasis to occur in the diabetic retina
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in macula densa, increasing luminal NaCl induces superoxide anion production during tubuloglomerular feedback. Superoxide anion generated by the macula densa is primarily derived from NAD(P)H oxidase and is induced by depolarization
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application of HIV regulatory protein Tat to microglia or macrophages causes dose- and time-dependent increases in superoxide formation that are prevented by both pharmacologic NADPH oxidase inhibitors and by specific decoy peptides gp91ds. Inhibition of NADPH oxidase attenuates Tat-induced release of IL-6 and TNFalpha, and MCP-1, and decreases microglial-mediated neurotoxicity. Macrophages derived from NADPH oxidase deficient mice display reduced superoxide production, released lower levels of cytokines/chemokines, and induce less neurotoxicity in response to Tat compared to wild-type macrophages
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inhibition of subunit Nox4 expression by small interfering RNA reduces angiogenic responses, in both human microvascular and umbilical vein endothelial cells. Overexpression of wild-type Nox4 enhances, whereas expression of a dominant negative form of Nox4 suppresses the angiogenic responses in endothelial cells. These effects are mimicked by exogenous H2O2 and the antioxidant compound ebselen, respectively. Overexpression of Nox4 enhances receptor tyrosine kinase phosphorylation and the activation of extracellular signal-regulated kinase. Nox4 expression also promotes proliferation and migration of endothelial cells, and reduces serum deprivation-induced apoptosis
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rosiglitazone activates 5'-AMP-activated protein kinase which, in turn, prevents hyperactivity of NAD(P)H oxidase induced by high glucose, possibly through protein kinase C inhibition. Rosiglitazone protects endothelial cells against glucose-induced oxidative stress with an 5'-AMP-activated protein kinase-dependent and a PPARgamma-independent mechanism
medicine
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isoform Nox4 is expressed at high levels in white and brown preadipocytes. Differentiation into adipocytes results in a decrease in their NOX4 mRNA content. In intact adipose tissue, the majority of NOX4 expressing cells are localized within the preadipocyte containing stromal/vascular fracftion. Alterations in NOX4 expression reflects changes in the ratio of adipocyte/interstitial fractions
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reactive oxygen species produced upstream of Ca2+ influx by NADPH oxidase and downstream of Ca2+ influx by the mitochondria regulate the proinflammatory response of mast cells
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rosuvastatin reduces systolic blood pressure in spontaneously hypertensive rats but does not change plasma lipid levels. Rosuvastatin treatment in spontaneously hypertensive rats significantly decreases reactive oxygen species levels , NAD(P)H activity in retinal ganglion cells, and increases retinal plasmalogen content in spontaneously hypertensive rats, but does not modify the electroretinogram response
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wild-type mice with myocardial infarction display significantly increased gp91phox and 3-nitrotyrosine in the infarcted myocardium, accumulated macrophages and myofibroblasts at the infarct site, abundant apoptotic myocytes primarily at border zones on day 3, and numerous apoptotic inflammatory/myofibroblasts in the later stages. Transforming growth factor 1, tissue inhibitor of metalloprotease 2, and type 1 collagen gene expression is increased, collagen volume in the infarcted myocardium continuously increases, and noninfarcted myocardium displays hypertrophy. Compared to wild-type mice with myocardial infarction, subunit gp91phox knockout mice do not display significant difference in infarct size/thickness, cardiac hypertrophy, myocyte apoptosis, inflammatory/fibrogenic responses, as well as cardiac oxidative stress
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after 14 days, local treatment with apocynin via the adventitia, reduces superoxide generation. Apocynin significantly reduces neointima formation and proliferation of cells in both the neointima and adventitia. Nitric oxide-dependent vasorelaxation to acetylcholine, which is normally impaired in collared arteries, is improved, and apocynin suppresses the endothelial expression of intracellular adhesion molecule- and vascular cell adhesion molecule-
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in sarcoplasmic reticulum vesicles isolated after exercise and tachycardia, increase in NAD(P)H oxidase activity, ryanodine receptor-2 S-glutathionylation, and calcium release rates. Apocynin prevents the increase in ryanodine receptor-2 S-glutathionylation, reduced calcium release activity, and completely prevents the protective effects of exercise and tachycardia on infarct size
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hypoosmotic swelling of cardiac myocytes activates volume-sensitive Cl- current via the angiotensin II-reactive oxygen species signalling cascade. In several models of cardiac disease, volume-sensitive Cl- current is persistently activated
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in peripheral blood lymphocytes from children with acute asthma, activity of NAD(P)H oxidase is significantly increased. Plasma levels of malondialdehyde, and nitric oxide are also markedly elevated, while catalase activity is decreased. Treatment of lymphocytes with salbutamol at 10 microg per ml, prevents the attenuation of catalase activity but significantly increases the levels of nitroc oxide and NAD(P)H oxidase activity. Levels of isoform NOX-1 mRNA are significantly increased in peripheral blodd lymphocytes following treatment with NO donor, S-nitroso-N-acetyl penicillamine. Subunit gp91phox protein is also two- to threefold increased following treatment with S-nitroso-N-acetyl penicillamine and leads to increased NAD(P)H oxidase activity
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hydrophobic, proapoptotic bile salts induce hepatocyte shrinkage largely through NADPH oxidase-derived oxidative stress. Because cell shrinkage in turn activates NADPH oxidase, which blunts cell volume recovery, a vicious cycle ensues between oxidative stress and cell shrinkage, which propagates CD95 activation and may finally lead to apoptosis
medicine
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after myocardial infarction, NAD(P)H oxidase activity is markedly increased in remote left ventricular myocardium of wild-type mice but not in mice deficient in subunit p47phox. Increased myocardial xanthine oxidase activity is observed in wild-type, but not in p47phox-deficient mice after myocardial infarction. Left ventricular cavity dilatation and dysfunction 4 weeks after infarction are markedly attenuated in p47phox-deficient mice and cardiomyocyte hypertrophy, apoptosis, and interstitial fibrosis are substantially reduced as compared with wild-type. The survival rate is markedly higher in mice deficient in subunit p47phox
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in lungs from patients with idiopathic pulmonary arterial hypertension, expression levels of NOX4, which is localized in the vessel media, are 2.5-fold upregulated
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hypoxic conditions lead to upregulation exclusively of NOX4 mRNA in lung, concomitant with increased levels in microdissected pulmonary arterial vessels. NOX4 mRNA and protein are localized predominantly in the media of small pulmonary arteries, with increased labeling intensities after chronic exposure to hypoxia. In isolated pulmonary arterial smooth muscle cells, NOX4 is localized primarily to the perinuclear space
medicine
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overweight and obese adults demonstrate increased vascular endothelial expression of NAD(P)H oxidase subunit p47phox and evidence of endothelial oxidative stress, with selective compensatory upregulation of antioxidant enzymes and Ser1177-phosphorylated endothelial nitric oxide synthase. Endothelin-1 and nuclear factor kappaB protein expression also appear to be elevated in obese compared with lean adults
medicine
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diabetes-induced translocation of protein kinase C, specifically PKC-alpha to renal membranes is associated with increased NADPH-dependent superoxide production. In both diabetic animals and in advanced glycation end products-treated mesangial cells, blockade of NADPH oxidase or PKC-alpha attenuates cytosolic superoxide and protein kinase C activation and increases vascular endothelial growth factor
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NADPH oxidase is involved in killing of Candida albicans by dendritic cells, which is increased by interferon-alpha or interferon-gamma. However, Candida escapes the oxidative damage by inhibiting NADPH oxidase and by entering dendritic cells through receptors not involved in NADPH oxidase activation
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increased oxidative stress in the vasculature of streptozotocin-induced diabetic apoE-deficient mice is linked to changes in endothelial nitric oxide synthase, superoxide dismutase and NADPH oxidase expression
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chronic administration of agents that induce hypertension can also produce changes in the subcellular localization in subunit p47phox in dorsomedial nucleus tractus solitarius neurons. Systemic hypertension may produce alterations in the trafficking of proteins associated with superoxide production in central autonomic neurons. Administration of angiotensin over 7 days, which produces elevated systemic blood pressure, is associated with a redistribution of p47phox immunolabeling away from intracellular organelles in the distal dendritic compartment, and toward non-vesicular targets in less distal, intermediate areas of dorsomedial nucleus tractus solitarius neurons. Chronic administration of phenylephrine, which produces increases in systolic blood pressure, is associated with a repartitioning of p47phox immunolabeling away from intracellular organelles in distal dendritic areas, andtoward the plasma membrane of intermediate dendritic areas of dorsomedial nucleus tractus solitarius neurons
medicine
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(pro)renin receptor is constitutively expressed in renal glomeruli and tubules. Expression of the receptor is upregulated in diabetes via enhancement of angiotensin subtype 1 receptor-NADPH oxidase activity
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isoobtusilactone A elicits a concentration-dependent growth impediment with IC50 value of 37.5 microM. Treated cells also display transient increase of reactive oxygen species during the earlier stage of the experiment, followed by the disruption of mitochondrial transmembrane potential. The presence of a reactive oxygen species scavenger N-acetyl-L-cysteine and the inhibitor of NADPH oxidase diphenyleneiodonium chloride block reactive oxygen species production and the subsequent apoptotic cell death
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treatment of animals by oral administration of isoobtusilactone A for two weeks does not result in significant difference between control animals and treated animals with respect to the body weight gain, the body weight ratio of liver, spleen and kidney, haematological and clinical chemistry parameters
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microinjection of lipopolysaccharide bilaterally into the rostral ventrolateral medulla induces progressive hypotension, bradycardia, and reduction in sympathetic vasomotor outflow. This is accompanied by an increase in superoxide anion production for 60-240 min, alongside phosphorylation of subunits p47phox or p67phox, upregulation of gp91phox or p47phox protein, and increase in Rac-1 or NADPH oxidase activity during 60-120 min, and a depression of mitochondrial respiratory enzyme activity during 120-240 min. Inhibition of NADPH oxidase or knockdown of the gp91phox or p47phox gene blunts the early phase of 60-150 min, coenzyme Q10 or mitochondrial KATP channel inhibitor antagonizes the delayed phase of 120-240 min of lipopolysaccharide-nduced increase in superoxide anion production in rostral ventrolateral medulla and cardiovascular depression
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induction of superoxide production by doxorubicin is much higher in hearts of wild-type mice than in subunit gp91phox knock-out mice. Superoxide production is similarly induced by addition of NADPH cytochrome P450 reductase
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glucose-mediated down-regulation of protein kinase G-I expression in vascular smooth muscle cells occurs through protein kinase C-dependent activation of NAD(P)H oxidase derived superoxide production, contributing to diabetes-associated vessel dysfunctions
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platelets and leukocytes from high cholesterol-fed mice exhibit elevated generation of reactive oxygen species compared to normal diet mice. Hypercholesterolemia-induced leukocyte recruitment is attenuated in Cu,Zn-superoxide dismutase transgenic, and NAD(P)H oxidase-knockout mice on high cholesterol diet. Platelets from NAD(P)H oxidase-knockout mice on high cholesterol diet exhibit low levels of adhesion comparable to those of wild-type on normal diet. Overexpression of Cu,Zn-superoxide dismutase or, to a lesser extent, NAD(P)H oxidase subunit gp91 deficiency restores arteriolar vasorelaxation responses toward normal diet wild-type levels
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in rabbits with heart failure induced by myocardial infarction, treatment with inhibitor apocynin reduces NADPH oxidase activity, subunit p47phox protein, oxidative stress, myocyte apoptosis, and Bax protein, increases Bcl-2 protein, and ameliorates left ventricular dilatation and dysfunction
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long-term survival mechanisms in niacin deficient HaCaT keratinocyte cells involve accumulation of reactive oxygen species and increased DNA damage with concomitant increase in expression and activity of NAD(P)H oxidase
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on a high-salt diet of 4% NaC1, male and obese rats have significantly higher mean arterial blood pressure relative to female and lean rats and reduced renal cortical nitric oxide synthase activity. Lean female rats have the highest outer medullary protein levels of several NADPH oxidase subunits, including gp91phox, p47phox, and p67phox, however, renal NADPH activity is not increased in lean females, but is significantly increased in obese rats of both sexes
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aortas of transgenic rats harboring the mouse renin transgene exhibit greater NADPH oxidase activity, reactive oxygen species levels, C-reactive protein, tumor necrosis factor-alpha expression, apoptosis, and wall thickness, which are significantly attenuated by in vivo treatment with angiotensin type 1 receptor blockade by valsartan or the superoxide dismutase/catalase mimetic tempol
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intrarenal infusions of angiotensin II both in vitro and in vivo increase renal vascular resistance, and alpha2-adrenoceptor agonist UK14,304 enhances this response. The interaction between angiotensin II and UK14,304 is blocked by inhibitors of NAD(P)H oxidase
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single nucleotide polymorphisms 242C/T and 640A/G in the gene encoding p22phox subunit of NAD(P)H oxidase are marginally significantly associated with asthma, but single nucleotide polymorphisms 640A/G shows a significant association with sensitization to two allergens tested. Haplotype 930G/242T/640A is associated with an increased risk of asthma
medicine
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expression of isoform Nox4 mRNA in glioblastomas of WHO grade IV is significantly higher than other astrocytomas of WHO grades II and III. Knock-down of isoform Nox4 expression by RNAi results in cell-growth inhibition and enhances induction of apoptosis by chemotherapeutic agents in cultured glioma cell lines
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experimental model of spontaneous intracranial hemorrhage in transgenic mice expressing human renin and human angiotensinogen treated with high-salt diet and Nomega-nitro-L-arginine methyl ester. In these mice, NAD(P)H oxidase activity is significantly increased. Increased enzyme activity preceeds signs of spontaneous intracranial hemorrhage and increases further whith development of intracranial hemorrhage
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neutropjhil NAD(P)H oxidase activation, induced by hemorrhagic shock/resuscitation and as mediated by high-mobility group box HMGB1/TLR4 signaling, is an important mechanism responsible for hemorrhagic shock/resuscitation-mediated inflammation and organ injury after hemorrhage
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pivotal role of myeloid Src family kinases and complement receptor 3 in mounting an effective defense against infection with Streptococcus pneumonia by regulating phagocytosis and NADPH oxidase-dependent superoxide production. Leukocyte recruitment into the cerebrospinal fluid space and bacterial clearance is hampered in mice deficient in all three myeloid Src family kinases during pneumococcal meningitis. The mice develop increased intracranial pressure and a worse clinical outcome with increased neurologic deficits and mortality, compared with wildtype mice. In neutrophils of mice deficient for myeloid Src family kinases p59/61hck, p58c-fgr, and p53/56lyn, phosphorylation of NAD(P)H oxidase subunit p40phox is absent, indicating a defect in enzyme activation
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the morphinan analog, sinomenine inhibits NAD(P)H oxidase cytosolic subunit p47phox translocation to the cell membrane and thus reduces lipopolysaccharide-induced extracellular reactive oxygen species production. Sinomenine protects neuron-glial cell cultures at both micro- and sub-picomolar concentrations against dopaminergic neuron death, but not protection is seen at nanomolar concentrations
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N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2, 5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide i.e. FLZ, squamosamide derivative. FLZ inhibits the translocation of the cytosolic subunit p47phox to the membrane and thus inhibits the activation of NAD(P)H oxidase. In vivo, FLZ significantly protects against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced dopaminergic neuronal loss
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after addition of thrombin to cell culture, expression of NADPH oxidase subunits p47phox and p67phox occurs, accompanied by up-regulation in the expression of cytosolic enzyme components Rac 1 and p67phox, and the translocation of cytosolic subunits p47phox and p67phox to the membrane. Thrombin-induced reactive oxygen species production, protein oxidation, and loss of cultured hippocampal neurons are partially attenuated by NADPH oxidase inhibition and/or by several antioxidants
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pharmacological inhibition or deficiency of human NADPH oxidase abolishes dermal-epidermal separation caused by autoantibodies and granulocytes ex vivo. Granulocyte-derived NADPH oxidase is a key molecular effector engaged by pathogenic autoantibodies and provides relevant targets for prevention of tissue damage in granulocyte-mediated autoimmune diseases
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neutrophil cytosolic factor 1-deficient mice lacking functional NADPH oxidase are resistant to skin blistering by the passive transfer of antibodies against type VII collagen. Recruitment of granulocytes into the skin is required for tissue injury, as demonstrated by the resistance to experimental blistering of wild-type mice depleted of neutrophils and of CD18-deficient mice. Granulocyte-derived NADPH oxidase is a key molecular effector engaged by pathogenic autoantibodies and provides relevant targets for prevention of tissue damage in granulocyte-mediated autoimmune diseases
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induction of sterile hyperinflammation by injection of fungal cell wall preparations in chronic granulomatous disease mouse model. Preparations from Aspergillus fumigatus, Candida albicans, or Saccharomyces cerevisiae cause prolonged and severe skin inflammation, but not preparations from bacteria such as Staphylococcus aureus, Pseudomonas aerginosa, or Escherichia coli. Components most responsible for the inflammatory effect are branched fungal beta-glucans
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incubation of microglial cultures in the presence of fibrillar amyloid beta1-42 induces the assembly and the activation of NADPH oxidase, and triggers the production of superoxide anion-derived reactive oxygen species. Pretreatment of microglia with melatonin dosedependently prevents the activation of NADPH oxidase and decreases the production of reactive oxygen species. Melatonin inhibits the phosphorylation of the p47phox subunit of NADPH oxidase via a PI3K/Akt-dependent signalling pathway, blocks the translocation of p47phox and p67phox subunit to the membrane, down-regulates the binding of p47phox to gp91phox, and impairs the assembly of NADPH oxidase
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treatment with peptidyl inhibitor gp91ds-tat reduces proliferation and migration of cultured microvascular endothelial cells
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analysis of pre-interventional intravascular ultrasound images and histological specimens obtained by directional coronary artherectomy of patients with atherosclerosis. Reactive oxygen positive area ratio in directional coronary artherectomy probes correlates positiviely with vessel cross-sectional area, and relative plaque area. The area immunopositive for subunit p22phox also correlates positively with vessel cross-sectional area, and relative plaque area
medicine
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pre-treatment of NB-4 cells with inhibitor diphenyleneiodinium blocks arsenic trioxide-induced apoptosis
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treatment of fibroblasts with tumor necrosis factor induces the formation of a signaling complex containing TNF-R1-associated death domain protein TRADD, receptor interacting protein RIP1, NAD(P)H oxidase Nox1, and the small GTPase Rac1. Formation of this complex plays a key role in tumor necrosis factor-induced necrotic cell death
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characterization of mutant V674G. Thyroid glands of mutant mice are goitrous and contain few normal follicles, anterior pituitaries are dysplastic. Serum thyroxine in homozygotes is about one-tenth the level of controls.. the weight of adult mutant mice is approximately half that of littermate controls, and serum IGF-I is reduced. The cochleae of mutant mice exhibit abnormalities characteristic of hypothyroidism, including a delayed formation of the inner sulcus and tunnel of Corti and an abnormally thickened tectorial membrane. Hearing thresholds of adult mutant mice are on average 50-60 decibels above those of controls
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apocynin reduces avascularity and apoptosis in the oxygen-indunced retinopathy model. The antioxidant properties of N-acetylcysteine are not effective in reducing intravitreous neovasicularization or avascular retina
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neuroblastoma cell, cells differentiated by retinoic acid die after exposure to glycated albumin, a model of advanced glycation end product-modified protein. Undifferentiated cells are resistant to glycated albumin. Differentiated cells pre-treated with NAD(P)K oxidase inhibitor diphenyleneiodinium or with rottlerin, an inhibitor of protein kinase C delta, are able to prevent neuronal death induced by glycated albumin
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study on the aggregation of platelets from high-risk cardiac patients with aspirin resistance in presence of adenosine diphosphate, collagen, and epinephrine. Inhibition of NAD(P)H oxidase effectively suppresses collagen and epinephrine-induced aggregation
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inhibition of NAD(P)H oxidase by apocynin in ischemia-induced mice prevents blood-brain barrier damage in the ischemic hemisphere I after reperfusion. In mice deficient in subunit gp91phox, middle cerebral artery occlusion-induced blood-brain barrier disruption and lesion volume in ischemia-induced animals are largely attenuated. Activation of NAD(P)H oxidase promotes cerebral reactive oxygen species formation, which then leads to Rho kinase-mediated endothelial cell contraction and disruption of the blood-brain barrier
medicine
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in brain capillary endothelial cells, hypoxia/reoxygenation induces translocation of the NAD(P)H oxidase activator Rac-1 to the membrane. Inhibition of Rac-1 prevents the ischemia/reperfusion-induced blood-brain barrier disruption. Activation of NAD(P)H oxidase promotes cerebral reactive oxygen species formation, which then leads to Rho kinase-mediated endothelial cell contraction and disruption of the blood-brain barrier
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mice lacking the NAD(P)H oxidase gp91phox subunit respond to exposure to single-walled carbon nanotubes with a marked accumulation of polymorphnuclear neutrophils and elevated levels of apoptotic cells in the lungs, production of pro-inflammatory cytokines, decreased production of the anti-inflammatory and pro-fibrotic cytokine, TGF-beta, and significantly lower levels of collagen deposition
medicine
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in obese, diabetic, leptin-receptor deficient db-/db- mice, mRNA levels of enzyme subunits Nox-1, Nox-2, and Nox-4 as well as Nox-2 protein expression are elevated, whereas aortic Cu/Zn superoxide dismutase protein and PPARgamma mRNA levels are reduced
medicine
inactivating mutations of Duox2 are linked to congenital hypothyroidism, and epigenetic silencing of Duox is frequently observed in lung cancer
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chronic granulomatous disease is a rare inherited immunodeficiency syndrome caused by mutations in four genes encoding essential nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex components. Clinical, functional, and molecular investigation of chronic granulomatous disease in nine Jordanian families
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Burkholderia cenocepacia resides in macrophage vacuoles displaying an altered recruitment of the NADPH oxidase complex at the phagosomal membrane. This phenomenon may contribute to preventing the efficient clearance of this opportunistic pathogen from the infected airways of susceptible patients
medicine
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as NAD(P)H oxidase activation may have dual actions in diabetes, selective targeting of the deleterious effects of sustained NAD(P)H oxidase activation, such as eNOS uncoupling, mitochondrial dysfunction, and impaired antioxidant gene expression, may prove beneficial in the treatment of diabetes
medicine
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as NAD(P)H oxidase activation may have dual actions in diabetes, selective targeting of the deleterious effects of sustained NAD(P)H oxidase activation, such as eNOS uncoupling, mitochondrial dysfunction, and impaired antioxidant gene expression, may prove beneficial in the treatment of diabetes
medicine
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as NAD(P)H oxidase activation may have dual actions in diabetes, selective targeting of the deleterious effects of sustained NAD(P)H oxidase activation, such as eNOS uncoupling, mitochondrial dysfunction, and impaired antioxidant gene expression, may prove beneficial in the treatment of diabetes
medicine
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as NAD(P)H oxidase activation may have dual actions in diabetes, selective targeting of the deleterious effects of sustained NAD(P)H oxidase activation, such as eNOS uncoupling, mitochondrial dysfunction, and impaired antioxidant gene expression, may prove beneficial in the treatment of diabetes
medicine
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NADPH oxidase type 4 is a major source of oxidative stress and an effective therapeutic target in acute stroke
medicine
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NADPH oxidase type 4 is a major source of oxidative stress and an effective therapeutic target in acute stroke
LINKS TO OTHER DATABASES (specific for EC-Number 1.6.3.1)
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