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Information on EC 1.6.3.1 - NAD(P)H oxidase (H2O2-forming) and Organism(s) Mus musculus and UniProt Accession Q672J9
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1.6.3.1 NAD(P)H oxidase (H2O2-forming)IUBMB Comments
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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Word Map
- 1.6.3.1
- endothelial
- neutrophil
- artery
- p22phox
- dismutase
- angiotensin
- cardiovascular
- apocynin
- hypertension
- oxidases
- nicotinamide
- granulomatous
- cardiac
- fibrosis
- aortic
- atherosclerosis
- catalase
- sod
- leukocyte
- monocyte
-
chemiluminescence
- tnf
- pkc
-
phorbol
- diphenyleneiodonium
-
ii-induced
- iodonium
-
diphenylene
- myeloperoxidase
-
endothelium-dependent
- hypothyroidism
-
oxidase-derived
-
renin-angiotensin
- fmlp
- dihydroethidium
- losartan
-
tempol
- lucigenin
-
nitrotyrosine
- peroxynitrite
-
microbicidal
-
oxidase-dependent
-
vsmcs
-
flavocytochrome
- rac2
- medicine
-
ros-generating
- tiron
-
oxidase-mediated
- synthesis
- agriculture
-
fmlp-induced
- thyroperoxidase
- industry
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
nad(p)h oxidase, p47phox, gp91phox, nadph-oxidase, p67phox, duox2, duox1, nadph oxidase 4, phagocyte nadph oxidase, nadph oxidase 2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dual oxidase
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-
-
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Duox
-
-
-
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Duox2
large NOX
-
-
-
-
LNOX
-
-
-
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NADPH oxidase
NOX1
Nox2
NOX3
Nox4
p138 thyroid-oxidase
-
-
-
-
p138tox
-
-
-
-
ThOX
-
-
-
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ThOX2
-
-
-
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thyroid NADPH oxidase
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-
-
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thyroid oxidase
-
-
-
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thyroid oxidase 2
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-
-
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NADPH oxidase
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
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oxidation
-
-
-
-
reduction
-
-
-
-
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.
CAS REGISTRY NUMBER
COMMENTARY
9032-22-8
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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
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
-
-
?
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
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-
?
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
-
-
?
NATURAL SUBSTRATE
NATURAL 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
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
-
-
?
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
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(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
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
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
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hemin
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hemin treatment increases hemin oxidase-1 expression and activity in aorta and kidney of apolipoprotein Edeficient mice and significantly reduces both NADPH oxidase activity and superoxide generation in situ
N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2, 5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide
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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
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
sepiapterin
-
induction of oxidative stress, p22phox mRNA, endothelial nitric oxide synthase mRNA, and protein by glucose are lowered by concurrent incubation with sepiapterin
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
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
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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
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
-
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
-
selective NADPH oxidase inhibitor, inhibition of NADPH oxidase protects photoreceptors from light-induced degeneration
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
diphenyleneiodonium
-
treatment significantly decreases angiotensin II-induced endothelin-1 RNA and peptide expression, superoxide production as well as collagen expression
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
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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
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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
-
angiotensin II
-
potent stimulator of NAD(P)H oxidase O2- production in the vasculature
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
HIV regulatory protein Tat
-
NADPH oxidase mediates Tat-induced superoxide release in microglia and macrophages
-
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
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
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
-
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
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
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
-
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
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
-
additional information
-
superoxide production is induced by addition of NADPH cytochrome P450 reductase
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
cochlear and vestibular system, NOX3 is highly expressed in specific portions of the inner ear
-
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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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
-
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
-
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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depleting Rac1 (a component of NADPH oxidase) in mouse rod photoreceptors protects them from photo-oxidative stress without affecting their structure or function
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NAD(P)H oxidase may have a role in the structural arrangement and mechanical properties of the airway tissue
-
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
-
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
-
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
-
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
-
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
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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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
expression of cytosolic subunits of NAD(P)H oxidase p47phox and p67phox is not altered by hypercholesterolemia
-
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
inhibition of NAD(P)H oxidase abolishes endothelial dysfunction in AMP-activated protein kinase alpha2-deficient mice
malfunction
-
lentiviral silencing of Nox4 in an Ang2-sufficient bEnd cell line decreases Ang2 mRNA levels and greatly impairs hemangioma growth in vivo
malfunction
-
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
-
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
physiological function
-
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
-
increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes
physiological function
-
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
-
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
-
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
-
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
NADPH oxidases (NOX2/NOX4) and inducible nitric oxide synthase (iNOS) derived oxidative stress play a key role in psoriasis induced kidney dysfunction. NADPH oxidase (NOX2 and NOX4) isoforms, and inducible nitric oxidase synthase (iNOS) are elevated in the renal tissue under inflammatory conditions such as acute kidney injury and chronic kidney disease. These enzymes are capable of producing reactive oxygen species (ROS) in large quantities under inflammatory conditions, which may cause oxidative damage to biological macromolecules such as lipids, proteins and nucleic acids leading to malfunction of cellular structures through dysregulation of ion pumps, and enzymatic activity
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). NOX3_MOUSE
568
0
64495
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
additional information
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
V674G
-
the mutation is associated with severe congenital hypothyroidism. The mutant enzyme fails to release extracellular H2O2
additional information
-
aortic rings from mice deificient in subunit p47phox are more sensitive to apocynin-induced dilation than wild-type aortic rings
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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 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
-
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
-
NOX2-deficient mice serve as chronic granulomatous disease mouse model
additional information
-
a C242T mutation in the p22phox gene is associated with insulin resistance in non-diabetic subjects
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
-
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%
-
investigated the effect of imiquimod (IMQ)-induced psoriatic inflammation on kidney function and inflammation in a murine model. Psoriatic inflammation in mice is associated with kidney dysfunction as reflected by increased serum creatinine and blood urea nitrogen. Kidney dysfunction is paralleled by upregulation of reactive oxygen species (ROS) generating enzymes such as NOX2, NOX4 and iNOS
ischemia/reperfusion injury stimulates the expression of a 28000 Da NOX4 spliced isoform
-
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 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
-
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 expression of isoforms NOX2 and NOX4 is increased after spinal cord injury
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
medicine
-
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
medicine
-
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
medicine
-
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
medicine
-
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
medicine
-
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
-
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
-
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
-
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
medicine
-
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
medicine
-
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
medicine
-
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
medicine
-
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
-
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
medicine
-
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
-
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
-
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
medicine
-
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
medicine
-
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
medicine
-
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
medicine
-
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
medicine
-
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
medicine
-
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
medicine
-
vascular cell adhesion molecule-1 induction of NADPH oxidase in the endothelium is necessary for the eosinophil recruitment during allergic inflammation
medicine
-
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
medicine
-
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
medicine
-
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
-
NADPH oxidase type 4 is a major source of oxidative stress and an effective therapeutic target in acute stroke
medicine
-
in apolipoprotein E-knockout mice, aequous extract of Tessaria absinthioides and Prosopis strombulifera significantly reduce triglycerides and lipid peroxidation, increase plasma total antioxidant status, and improve glutathione peroxidase activity in the liver. Under high-fat diet, both extracts are able to inhibit O2 anion generation in the aortic tissue and cause a significant regression of atheroma plaques
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Banfi, B.; Clark, R.A.; Steger, K.; Krause, K.H.
Two novel proteins activate superoxide generation by the NADPH oxidase NOX1
J. Biol. Chem.
278
3510-3513
2003
Mus musculus (Q8CIZ9)
Banfi, B.; Malgrange, B.; Knisz, J.; Steger, K.; Dubois-Dauphin, M.; Krause, K.H.
NOX3, a superoxide-generating NADPH oxidase of the inner ear
J. Biol. Chem.
279
46065-46072
2004
Mus musculus (Q672J9), Rattus norvegicus (Q672K1)
Hidalgo, C.; Sanchez, G.; Barrientos, G.; Aracena-Parks, P.
A transverse tubule NADPH oxidase activity stimulates calcium release from isolated triads via ryanodine receptor type 1 S -glutathionylation
J. Biol. Chem.
281
26473-26482
2006
Mus musculus
Chen, J.X.; Zeng, H.; Tuo, Q.H.; Yu, H.; Meyrick, B.; Aschner, J.L.
NADPH oxidase modulates myocardial Akt, ERK1/2 activation, and angiogenesis after hypoxia-reoxygenation
Am. J. Physiol. Heart Circ. Physiol.
292
H1664-H1674
2007
Mus musculus, Sus scrofa
Wolfort, R.M.; Stokes, K.Y.; Granger, D.N.
CD4+ T lymphocytes mediate hypercholesterolemia-induced endothelial dysfunction via a NAD(P)H oxidase-dependent mechanism
Am. J. Physiol. Heart Circ. Physiol.
294
H2619-H2626
2008
Mus musculus
Abdala-Valencia, H.; Earwood, J.; Bansal, S.; Jansen, M.; Babcock, G.; Garvy, B.; Wills-Karp, M.; Cook-Mills, J.M.
Nonhematopoietic NADPH oxidase regulation of lung eosinophilia and airway hyperresponsiveness in experimentally induced asthma
Am. J. Physiol. Lung Cell. Mol. Physiol.
292
L1111-L1125
2007
Mus musculus
Chitano, P.; Wang, L.; Mason, S.N.; Auten, R.L.; Potts, E.N.; Foster, W.M.; Sturrock, A.; Kennedy, T.P.; Hoidal, J.R.; Murphy, T.M.
Airway smooth muscle relaxation is impaired in mice lacking the p47phox subunit of NAD(P)H oxidase
Am. J. Physiol. Lung Cell. Mol. Physiol.
294
L139-L148
2008
Mus musculus
Turchan-Cholewo, J.; Dimayuga, V.M.; Gupta, S.; Gorospe, R.M.; Keller, J.; Bruce-Keller, A.J.
NADPH oxidase drives cytokine and neurotoxin release from microglia and macrophages in response to HIV-Tat
Antioxid. Redox Signal.
11
193-204
2008
Mus musculus
Ostanin, D.V.; Barlow, S.; Shukla, D.; Grisham, M.B.
NADPH oxidase but not myeloperoxidase protects lymphopenic mice from spontaneous infections
Biochem. Biophys. Res. Commun.
355
801-806
2007
Mus musculus
Catarzi, S.; Giannoni, E.; Favilli, F.; Meacci, E.; Iantomasi, T.; Vincenzini, M.T.
Sphingosine 1-phosphate stimulation of NADPH oxidase activity: relationship with platelet-derived growth factor receptor and c-Src kinase
Biochim. Biophys. Acta
1770
872-883
2007
Mus musculus
Mouche, S.; Mkaddem, S.B.; Wang, W.; Katic, M.; Tseng, Y.H.; Carnesecchi, S.; Steger, K.; Foti, M.; Meier, C.A.; Muzzin, P.; Kahn, C.R.; Ogier-Denis, E.; Szanto, I.
Reduced expression of the NADPH oxidase NOX4 is a hallmark of adipocyte differentiation
Biochim. Biophys. Acta
1773
1015-1027
2007
Mus musculus
Inoue, T.; Suzuki, Y.; Yoshimaru, T.; Ra, C.
Reactive oxygen species produced up- or downstream of calcium influx regulate proinflammatory mediator release from mast cells: role of NADPH oxidase and mitochondria
Biochim. Biophys. Acta
1783
789-802
2008
Mus musculus
Miller, R.L.; Sun, G.Y.; Sun, A.Y.
Cytotoxicity of paraquat in microglial cells: Involvement of PKCdelta- and ERK1/2-dependent NADPH oxidase
Brain Res.
1167
129-139
2007
Mus musculus
Zhao, W.; Zhao, D.; Yan, R.; Sun, Y.
Cardiac oxidative stress and remodeling following infarction: role of NADPH oxidase
Cardiovasc. Pathol.
18
156-166
2008
Mus musculus
An, S.J.; Boyd, R.; Zhu, M.; Chapman, A.; Pimentel, D.R.; Wang, H.D.
NADPH oxidase mediates angiotensin II-induced endothelin-1 expression in vascular adventitial fibroblasts
Cardiovasc. Res.
75
702-709
2007
Mus musculus
Schlueter, T.; Steinbach, A.C.; Steffen, A.; Rettig, R.; Grisk, O.
Apocynin-induced vasodilation involves Rho kinase inhibition but not NADPH oxidase inhibition
Cardiovasc. Res.
80
271-279
2008
Mus musculus, Rattus norvegicus
Becker, S.; Reinehr, R.; Graf, D.; vom Dahl, S.; Haeussinger, D.
Hydrophobic bile salts induce hepatocyte shrinkage via NADPH oxidase activation
Cell. Physiol. Biochem.
19
89-98
2007
Mus musculus
Doerries, C.; Grote, K.; Hilfiker-Kleiner, D.; Luchtefeld, M.; Schaefer, A.; Holland, S.M.; Sorrentino, S.; Manes, C.; Schieffer, B.; Drexler, H.; Landmesser, U.
Critical role of the NAD(P)H oxidase subunit p47phox for left ventricular remodeling/dysfunction and survival after myocardial infarction
Circ. Res.
100
894-903
2007
Mus musculus
Mittal, M.; Roth, M.; Koenig, P.; Hofmann, S.; Dony, E.; Goyal, P.; Selbitz, A.C.; Schermuly, R.T.; Ghofrani, H.A.; Kwapiszewska, G.; Kummer, W.; Klepetko, W.; Hoda, M.A.; Fink, L.; Haenze, J.; Seeger, W.; Grimminger, F.; Schmidt, H.H.; Weissmann, N.
Hypoxia-dependent regulation of nonphagocytic NADPH oxidase subunit NOX4 in the pulmonary vasculature
Circ. Res.
101
258-267
2007
Homo sapiens, Mus musculus
Ding, H.; Hashem, M.; Triggle, C.
Increased oxidative stress in the streptozotocin-induced diabetic apoE-deficient mouse: changes in expression of NADPH oxidase subunits and eNOS
Eur. J. Pharmacol.
561
121-128
2007
Mus musculus
Deng, S.; Kruger, A.; Kleschyov, A.L.; Kalinowski, L.; Daiber, A.; Wojnowski, L.
Gp91phox-containing NAD(P)H oxidase increases superoxide formation by doxorubicin and NADPH
Free Radic. Biol. Med.
42
466-473
2007
Mus musculus
Stokes, K.Y.; Russell, J.M.; Jennings, M.H.; Alexander, J.S.; Granger, D.N.
Platelet-associated NAD(P)H oxidase contributes to the thrombogenic phenotype induced by hypercholesterolemia
Free Radic. Biol. Med.
43
22-30
2007
Mus musculus
Ribe, D.; Sawbridge, D.; Thakur, S.; Hussey, M.; Ledent, C.; Kitchen, I.; Hourani, S.; Li, J.M.
Adenosine A2A receptor signaling regulation of cardiac NADPH oxidase activity
Free Radic. Biol. Med.
44
1433-1442
2008
Mus musculus
Datla, S.R.; Dusting, G.J.; Mori, T.A.; Taylor, C.J.; Croft, K.D.; Jiang, F.
Induction of heme oxygenase-1 in vivo suppresses NADPH oxidase derived oxidative stress
Hypertension
50
636-642
2007
Homo sapiens, Mus musculus, Rattus norvegicus
Babilonia, E.; Lin, D.; Zhang, Y.; Wei, Y.; Yue, P.; Wang, W.H.
Role of gp91phox -containing NADPH oxidase in mediating the effect of K restriction on ROMK channels and renal K excretion
J. Am. Soc. Nephrol.
18
2037-2045
2007
Mus musculus
Nakashima, T.; Iwashita, T.; Fujita, T.; Sato, E.; Niwano, Y.; Kohno, M.; Kuwahara, S.; Harada, N.; Takeshita, S.; Oda, T.
A prodigiosin analogue inactivates NADPH oxidase in macrophage cells by inhibiting assembly of p47phox and Rac
J. Biochem.
143
107-115
2008
Mus musculus
Block, K.; Gorin, Y.; Hoover, P.; Williams, P.; Chelmicki, T.; Clark, R.A.; Yoneda, T.; Abboud, H.E.
NAD(P)H oxidases regulate HIF-2alpha protein expression
J. Biol. Chem.
282
8019-8026
2007
Homo sapiens, Mus musculus
Roepstorff, K.; Rasmussen, I.; Sawada, M.; Cudre-Maroux, C.; Salmon, P.; Bokoch, G.; van Deurs, B.; Vilhardt, F.
Stimulus-dependent regulation of the phagocyte NADPH oxidase by a VAV1, Rac1, and PAK1 signaling axis
J. Biol. Chem.
283
7983-7993
2008
Mus musculus
Ding, H.; Aljofan, M.; Triggle, C.R.
Oxidative stress and increased eNOS and NADPH oxidase expression in mouse microvessel endothelial cells
J. Cell. Physiol.
212
682-689
2007
Mus musculus
Wakisaka, Y.; Miller, J.D.; Chu, Y.; Baumbach, G.L.; Wilson, S.; Faraci, F.M.; Sigmund, C.D.; Heistad, D.D.
Oxidative stress through activation of NAD(P)H oxidase in hypertensive mice with spontaneous intracranial hemorrhage
J. Cereb. Blood Flow Metab.
28
1175-1185
2008
Mus musculus
Fan, J.; Li, Y.; Levy, R.M.; Fan, J.J.; Hackam, D.J.; Vodovotz, Y.; Yang, H.; Tracey, K.J.; Billiar, T.R.; Wilson, M.A.
Hemorrhagic shock induces NAD(P)H oxidase activation in neutrophils: role of HMGB1-TLR4 signaling
J. Immunol.
178
6573-6580
2007
Mus musculus
Paul, R.; Obermaier, B.; Van Ziffle, J.; Angele, B.; Pfister, H.W.; Lowell, C.A.; Koedel, U.
Myeloid Src kinases regulate phagocytosis and oxidative burst in pneumococcal meningitis by activating NADPH oxidase
J. Leukoc. Biol.
84
1141-1150
2008
Mus musculus
Zhang, D.; Hu, X.; Wei, S.; Liu, J.; Gao, H.; Qian, L.; Wilson, B.; Liu, G.; Hong, J.
Squamosamide derivative FLZ protects dopaminergic neurons against inflammation-mediated neurodegeneration through the inhibition of NADPH oxidase activity
J. Neuroinflammation
5
21
2008
Mus musculus, Rattus norvegicus
Chiriac, M.T.; Roesler, J.; Sindrilaru, A.; Scharffetter-Kochanek, K.; Zillikens, D.; Sitaru, C.
NADPH oxidase is required for neutrophil-dependent autoantibody-induced tissue damage
J. Pathol.
212
56-65
2007
Homo sapiens, Mus musculus
Schaeppi, M.; Deffert, C.; Fiette, L.; Gavazzi, G.; Herrmann, F.; Belli, D.; Krause, K.H.
Branched fungal beta-glucan causes hyperinflammation and necrosis in phagocyte NADPH oxidase-deficient mice
J. Pathol.
214
434-444
2008
Mus musculus
Teixeira, C.E.; Priviero, F.B.; Webb, R.C.
Effects of 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4-ylamine (BAY 41-2272) on smooth muscle tone, soluble guanylyl cyclase activity, and NADPH oxidase activity/expression in corpus cavernosum from wild-type, neuronal
J. Pharmacol. Exp. Ther.
322
1093-1102
2007
Mus musculus
Kim, Y.S.; Morgan, M.J.; Choksi, S.; Liu, Z.G.
TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death
Mol. Cell
26
675-687
2007
Mus musculus
Johnson, K.R.; Marden, C.C.; Ward-Bailey, P.; Gagnon, L.H.; Bronson, R.T.; Donahue, L.R.
Congenital hypothyroidism, dwarfism, and hearing impairment caused by a missense mutation in the mouse dual oxidase 2 gene, Duox2
Mol. Endocrinol.
21
1593-1602
2007
Mus musculus
Jang, H.J.; Hwang, S.; Cho, K.Y.; Kim, d.o..K.; Chay, K.O.; Kim, J.K.
Taxol induces oxidative neuronal cell death by enhancing the activity of NADPH oxidase in mouse cortical cultures
Neurosci. Lett.
443
17-22
2008
Mus musculus
Kahles, T.; Luedike, P.; Endres, M.; Galla, H.J.; Steinmetz, H.; Busse, R.; Neumann-Haefelin, T.; Brandes, R.P.
NADPH oxidase plays a central role in blood-brain barrier damage in experimental stroke
Stroke
38
3000-3006
2007
Mus musculus, Sus scrofa
Riganti, C.; Costamagna, C.; Doublier, S.; Miraglia, E.; Polimeni, M.; Bosia, A.; Ghigo, D.
The NADPH oxidase inhibitor apocynin induces nitric oxide synthesis via oxidative stress
Toxicol. Appl. Pharmacol.
228
277-285
2008
Mus musculus
Shvedova, A.A.; Kisin, E.R.; Murray, A.R.; Kommineni, C.; Castranova, V.; Fadeel, B.; Kagan, V.E.
Increased accumulation of neutrophils and decreased fibrosis in the lung of NADPH oxidase-deficient C57BL/6 mice exposed to carbon nanotubes
Toxicol. Appl. Pharmacol.
231
235-240
2008
Mus musculus
Hwang, J.; Kleinhenz, D.J.; Rupnow, H.L.; Campbell, A.G.; Thule, P.M.; Sutliff, R.L.; Hart, C.M.
The PPARgamma ligand, rosiglitazone, reduces vascular oxidative stress and NADPH oxidase expression in diabetic mice
Vascul. Pharmacol.
46
456-462
2007
Mus musculus
Luan, R.; Liu, S.; Yin, T.; Lau, W.B.; Wang, Q.; Guo, W.; Wang, H.; Tao, L.
High glucose sensitizes adult cardiomyocytes to ischaemia/reperfusion injury through nitrative thioredoxin inactivation
Cardiovasc. Res.
83
294-302
2009
Mus musculus
Yang, X.Q.; Chen, A.F.
High-cholesterol diet augments endothelial dysfunction via elevated oxidative stress and reduced tetrahydrobiopterin in Ins2(Akita) mice, an autosomal dominant mutant type 1 diabetic model
Clin. Exp. Pharmacol. Physiol.
36
764-769
2009
Mus musculus
Aram, G.; Potter, J.J.; Liu, X.; Wang, L.; Torbenson, M.S.; Mezey, E.
Deficiency of nicotinamide adenine dinucleotide phosphate, reduced form oxidase enhances hepatocellular injury but attenuates fibrosis after chronic carbon tetrachloride administration
Hepatology
49
911-919
2009
Mus musculus
Haruta, M.; Bush, R.A.; Kjellstrom, S.; Vijayasarathy, C.; Zeng, Y.; Le, Y.Z.; Sieving, P.A.
Depleting Rac1 in mouse rod photoreceptors protects them from photo-oxidative stress without affecting their structure or function
Proc. Natl. Acad. Sci. USA
106
9397-9402
2009
Mus musculus
Arora, S.; Vaishya, R.; Dabla, P.K.; Singh, B.
NAD(P)H oxidases in coronary artery disease
Adv. Clin. Chem.
50
65-86
2010
Oryctolagus cuniculus, Homo sapiens, Mus musculus
Matsushima, S.; Kinugawa, S.; Yokota, T.; Inoue, N.; Ohta, Y.; Hamaguchi, S.; Tsutsui, H.
Increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes
Am. J. Physiol. Heart Circ. Physiol.
297
H409-H416
2009
Mus musculus
Piwkowska, A.; Rogacka, D.; Jankowski, M.; Dominiczak, M.H.; Stepi?ski, J.K.; Angielski, S.
Metformin induces suppression of NAD(P)H oxidase activity in podocytes
Biochem. Biophys. Res. Commun.
393
268-273
2010
Mus musculus
Gao, L.; Mann, G.E.
Vascular NAD(P)H oxidase activation in diabetes: a double-edged sword in redox signalling
Cardiovasc. Res.
82
9-20
2009
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus
Ben Mkaddem, S.; Pedruzzi, E.; Werts, C.; Coant, N.; Bens, M.; Cluzeaud, F.; Goujon, J.; Ogier-Denis, E.; Vandewalle, A.
Heat shock protein gp96 and NAD(P)H oxidase 4 play key roles in Toll-like receptor 4-activated apoptosis during renal ischemia/reperfusion injury
Cell Death Differ.
17
1474-1485
2010
Mus musculus
Wang, S.; Zhang, M.; Liang, B.; Xu, J.; Xie, Z.; Liu, C.; Viollet, B.; Yan, D.; Zou, M.H.
AMPKalpha2 deletion causes aberrant expression and activation of NAD(P)H oxidase and consequent endothelial dysfunction in vivo: role of 26S proteasomes
Circ. Res.
106
1117-1128
2010
Homo sapiens, Mus musculus
Saitoh, Y.; Hongwei, W.; Ueno, H.; Mizuta, M.; Nakazato, M.
Telmisartan attenuates fatty-acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic beta-cells
Diabetes Metab.
35
392-397
2009
Mus musculus
Bhandarkar, S.S.; Jaconi, M.; Fried, L.E.; Bonner, M.Y.; Lefkove, B.; Govindarajan, B.; Perry, B.N.; Parhar, R.; Mackelfresh, J.; Sohn, A.; Stouffs, M.; Knaus, U.; Yancopoulos, G.; Reiss, Y.; Benest, A.V.; Augustin, H.G.; Arbiser, J.L.
Fulvene-5 potently inhibits NADPH oxidase 4 and blocks the growth of endothelial tumors in mice
J. Clin. Invest.
119
2359-2365
2009
Mus musculus
Kleinschnitz, C.; Grund, H.; Wingler, K.; Armitage, M.E.; Jones, E.; Mittal, M.; Barit, D.; Schwarz, T.; Geis, C.; Kraft, P.; et al
Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration
PLoS Biol.
8
e1000479
2010
Homo sapiens, Mus musculus
Zhao, R.; Le, K.; Moghadasian, M.H.; Shen, G.X.
Regulatory role of NADPH oxidase in glycated LDL-induced upregulation of plasminogen activator inhibitor-1 and heat shock factor-1 in mouse embryo fibroblasts and diabetic mice
Free Radic. Biol. Med.
61C
18-25
2013
Mus musculus, Mus musculus C57BL/6
Matsumoto, M.; Katsuyama, M.; Iwata, K.; Ibi, M.; Zhang, J.; Zhu, K.; Nauseef, W.M.; Yabe-Nishimura, C.
Characterization of N-glycosylation sites on the extracellular domain of NOX1/NADPH oxidase
Free Radic. Biol. Med.
68
196-204
2014
Homo sapiens, Mus musculus, Rattus norvegicus
Donko, A.; Morand, S.; Korzeniowska, A.; Boudreau, H.E.; Zana, M.; Hunyady, L.; Geiszt, M.; Leto, T.L.
Hypothyroidism-associated missense mutation impairs NADPH oxidase activity and intracellular trafficking of Duox2
Free Radic. Biol. Med.
73
190-200
2014
Mus musculus
Bermudez, S.; Khayrullina, G.; Zhao, Y.; Byrnes, K.R.
NADPH oxidase isoform expression is temporally regulated and may contribute to microglial/macrophage polarization after spinal cord injury
Mol. Cell. Neurosci.
77
53-64
2016
Mus musculus
Al-Harbi, N.O.; Nadeem, A.; Ansari, M.A.; Al-Harbi, M.M.; Alotaibi, M.R.; AlSaad, A.M.; Ahmad, S.F.
Psoriasis-like inflammation leads to renal dysfunction via upregulation of NADPH oxidases and inducible nitric oxide synthase
Int. Immunopharmacol.
46
1-8
2017
Mus musculus (Q9JHI8)
Quesada, I.; de Paola, M.; Alvarez, M.S.; Hapon, M.B.; Gamarra-Luques, C.; Castro, C.
Antioxidant and anti-atherogenic properties of Prosopis strombulifera and Tessaria absinthioides aqueous extracts modulation of NADPH oxidase-derived reactive oxygen species
Front. Physiol.
12
662833
2021
Mus musculus, Rattus norvegicus
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