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Information on EC 1.6.3.1 - NAD(P)H oxidase (H2O2-forming) and Organism(s) Homo sapiens and UniProt Accession Q9NRD8

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EC Tree
     1 Oxidoreductases
         1.6 Acting on NADH or NADPH
             1.6.3 With oxygen as acceptor
                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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Select one or more organisms in this record:
This record set is specific for:
Homo sapiens
UNIPROT: Q9NRD8
Word Map
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The taxonomic range for the selected organisms is: Homo sapiens
Synonyms
Atrbohc, AtrbohD NADPH oxidase, AtrbohF NADPH oxidase, BLI-3, dual oxidase, Duox, Duox-DuoxA NADPH oxidase, Duox1, Duox2, gp91phox, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dual oxidase
-
-
-
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Duox
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-
-
-
Duox-DuoxA NADPH oxidase
266838, 288116
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Duox1
Duox2
gp91phox
gp91phox/Nox2
247
-
large NOX
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-
-
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LNOX
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-
-
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NAD(P)H oxidase 4
247
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NADPH oxidase
NADPH oxidase 1
247
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NADPH oxidase 2
247
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NADPH oxidase 4
NADPH oxidase 5
247
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NADPH oxidase type 4
247
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p138 thyroid-oxidase
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-
-
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p138tox
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-
-
-
p47phox
247
subunit
p67phox
247
subunit
phagocyte NADPH oxidase
247
-
phox
247
-
renal oxidase
247
originally termed
renox
247
originally termed
ThOX
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-
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ThOX2
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-
-
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thyroid NADPH oxidase
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-
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thyroid oxidase
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-
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thyroid oxidase 2
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-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
NAD(P)H + H+ + O2 = NAD(P)+ + H2O2
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
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redox reaction
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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.
CAS REGISTRY NUMBER
COMMENTARY hide
9032-22-8
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
show the reaction diagram
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
show the reaction diagram
NADH + H+ + O2
NAD+ + H2O2
show the reaction diagram
NADPH + O2
NADP+ + O2-
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
show the reaction diagram
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
show the reaction diagram
NADH + H+ + O2
NAD+ + H2O2
show the reaction diagram
NADPH + H+ + O2
NADP+ + H2O2
show the reaction diagram
-
-
-
-
?
NADPH + O2
NADP+ + O2-
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADPH
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binding site
FMN
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can replace for FAD
NADPH
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
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heme iron
additional information
-
Mg2+ cannot substitute for Ca2+, metal binding/dissociation kinetics, overview
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(-)-epicatechin
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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 gallate
-
inhibition of intracellular reactive oxygen species generation
(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
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complete inhibition at 0.01 mM
(3Z)-3-(3,4-dihydroxybenzylidene)-5-nitro-1,3-dihydro-2H-indol-2-one
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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
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
-
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15-cis-(4-propyl-cyclohexyl)-16,17,18,19,20-pentanor-9-deoxy-9alpha,6-nitrilo-prostaglandin F1 methyl ester
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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
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93% inhibition at 0.01 mM
2,3,8,9-tetrahydroxy-5-[2-(phenylsulfonyl)benzyl]phenanthridin-6(5H)-one
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95% inhibition at 0.01 mM
2,4,5-trimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2,4-dimethyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
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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
-
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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
-
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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
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-
2-(2-chloro-4-fluorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]-pyridine-3,6(2H,5H)-dione
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2-(2-chloro-4-fluorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
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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
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2-(2-chlorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
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2-(2-chlorophenyl)-4-(2-fluorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
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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
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-
2-(2-chlorophenyl)-4-methyl-5-(3-phenylprop-2-yn-1-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
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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
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-
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-fluorophenyl)-4,5-dimethyl-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-(3-chlorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
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
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-
2-hydroxy-5-[(2-hydroxybenzyl)amino]benzoic acid
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89% inhibition at 0.01 mM
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
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3'-(or 4'-)methylluteolin
-
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3'-O-methyl epicatechin
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3,5,7-trihydroxy-2-(4-hydroxy-3-methylphenyl)-4H-chromen-4-one
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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
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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'-O-methyl epicatechin
-
-
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-amino-ethyl)-benzolsulphonyl-fluoride
-
-
4-(2-aminoethyl)-benzenesulfonyl fluoride
-
-
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-[(2,5-dihydroxybenzyl)amino]-2-hydroxybenzoic acid
-
82% inhibition at 0.01 mM
abruquinone C
-
-
apocynin
ATDITGPIILQTYRA
-
a peptide inhibitor derived from human p47phox
AYRRNSVRFL
-
inhibits NADPH oxidase activation
AYRRNSVRFVRFLN
-
a peptide inhibitor derived from human p47phox
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
bilirubin
-
bilirubin concentration-dependently reduces NADPH oxidase-dependent superoxide production stimulated by phorbol 12-myristate 13-acetate
Cdc42
-
a small monomeric GTPase, competitive inhibitor of Nox2, might also be a competitive inhibitor of Nox1
-
CERLVRFWRSQQKVV
-
a peptide inhibitor derived from human gp91phox/NOX2
COMT-methylated procyanidin B2
-
-
-
CSTRVRRQLDRNLTFHK
-
a peptide inhibitor derived from human gp91phox/NOX2
dihydrokaempferol
-
-
dihydrotamarixetin
-
-
diosmetin
-
-
diphenylene iodinium
-
treatment of NB-4 cells blocks basal generation of reactive oxygen species and arsenic trioxide-induced apoptosis
diphenylene iodinium chloride
-
enzyme inhibitor, pretreatment of cells completely blocks insulin-stimulated activation of hypoxia-inducible factor 1
diphenylene iodonium
diphenyleneiodonium
diphenyliodonium
-
-
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
Epicatechin gallate
-
-
epigallocatechin
-
-
epigallocatechin gallate
-
-
FAVHHDEEDVITG
-
a peptide inhibitor derived from human gp91phox/NOX2
FAVHHDEEKDVITG
-
-
ferulic acid
-
-
FIRHIALLGFEKRFV
-
a peptide inhibitor derived from human p47phox
FLRGSSACCSTRVRRQL
fulvene-5
-
-
GK-136901
-
inhibition of NOX1 and NOX4
gliotoxin
-
-
gomisin C
-
-
hesperetin
-
-
honokiol
IRNAHSIHQRSRKRL
-
a peptide inhibitor derived from human p47phox
ISNSESGPRGVHFIFNKENF
-
a peptide inhibitor derived from human gp91phox/NOX2
isorhamnetin
-
-
isorhamnetin glucuronide
-
-
KTIELQMKKKGFKM
-
a peptide inhibitor derived from human gp91phox/NOX2
LKLKKIYFYWLCRDTHAF
-
a peptide inhibitor derived from human gp91phox/NOX2
LKSVWYKYCN
-
a peptide inhibitor derived from human gp91phox/NOX2
LKSVWYKYCNN
-
a peptide inhibitor derived from human gp91phox/NOX2
magnolol
-
-
methimazol
-
partial
methyl 2-hydroxy-5-[(2-hydroxybenzyl)amino]benzoate
-
91% inhibition at 0.01 mM
ML171
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inhibition NOX1
N'1,N'2-bis[(E)-(2,3-dihydroxyphenyl)methylidene]ethanedihydrazide
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complete inhibition at 0.01 mM
N'1,N'2-bis[(E)-(3,4-dihydroxyphenyl)methylidene]ethanedihydrazide
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complete inhibition at 0.01 mM
N-(1-cyclohexylethyl)-4-phenylphthalazin-1-amine
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N-(3-aminophenyl)-N'-[1-(4-hydroxy-3-methoxyphenyl)ethyl]ethanediamide
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complete inhibition at 0.01 mM
N-[(3Z)-3-(4-hydroxy-3-methoxybenzylidene)-2-oxo-2,3-dihydro-1H-indol-5-yl]acetamide
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complete inhibition at 0.01 mM
N-[1-(3,4-dihydroxyphenyl)ethyl]-N'-(3-nitrophenyl)ethanediamide
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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
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N-[3-(4,5-dimethyl-3,6-dioxo-1,3,5,6-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)phenyl]acetamide
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N4-(3-aminophenyl)[1]benzothieno[3,2-d]pyrimidine-4,8-diamine
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98% inhibition at 0.01 mM
N4-(4-aminophenyl)[1]benzothieno[3,2-d]pyrimidine-4,8-diamine
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complete inhibition at 0.01 mM
naringenin
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neopterin
norathyriol
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Nox2ds-tat
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inhibition of NAOX1 and NOX2
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O-methyl-epicatechin
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inhibits endothelial NAD(P)H oxidase activity and prevents superoxide anion formation
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perhexilline
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phallacidin
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pretreatment of human pulmonary artery endothelial cells before induction of hyperoxia attenuates hyperoxia-induced cortical actin thickening and reactive oxygen species production
Phenylarsine oxide
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Plumbagin
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inhibition of NOX4
procyanidin B2
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acts both as a superoxide anion scavenger, and inhibitory to NAD(P)H oxidase, with apocynin-like mode of NADPH oxidase inhibition
prodigiosin
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propylthiouracil
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partial
prostaglandin E1
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inhibition of sodiumdodecylsulfate-induced activation in cell free extracts, 0.044 mM, 50% inhibition
PTKISRCPPHLLDFFK
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a peptide inhibitor derived from human p47phox
QRRRQARPGPQSPG
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a peptide inhibitor derived from human p47phox
quercetin 3-O-alpha-D-glucopyranoside
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complete inhibition at 0.01 mM
quercetin glucuronide
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-
RFVPSQHYVYMFLVK
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a peptide inhibitor derived from human p47phox
RGVHFIF
rosiglitazone
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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
RRNSVRFLQQRRRQA
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a peptide inhibitor derived from human p47phox
RRSSIRNAHSIHQRSRKRLS
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a peptide inhibitor derived from human p47phox
RSRKRLSQDAYRRNSVRF
RSRKRLSQDAYRRNSVRFLQQR
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a peptide inhibitor derived from human p47phox
SNSESGPRGVHFIFNKEN
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-
SRKRLSQDAYRRNS
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a peptide inhibitor derived from human p47phox
STRVRRQLDRNLTF
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a peptide inhibitor derived from human gp91phox/NOX2
tamarixetin
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-
VAS2870
VAS3947
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i.e. 3-benzyl-7-(2-oxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine, specific low micromolar NADPH oxidase inhibitor
VWYYRVYDIPPKFFYTRKLL
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a peptide inhibitor derived from human gp91phox/NOX2
WWFCQMKAKRGWIPA
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a peptide inhibitor derived from human p47phox
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(+)-(S)-2-(6-methoxynaphthalen-2-yl)propanoic acid
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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
2-(2-(2,6-dichlorophenylamino)-phenyl)acetic acid
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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
4-(4-methylsulfonylphenyl)-3-phenyl-5H-furan-2-one
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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-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
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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
5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b] pyridin-3-yl]-pyrimidin-4-ylamine
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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
A23127
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a calcium ionophore
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A23187
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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
angiotensin II
apigenin
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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
betaPix
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a Rac1 guanine nucleotide exchange factor, appears to be constitutively bound to Nox1 and essential for its activity
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cytochalasin D
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enhancement of basal and hyperoxia-induced reactive oxygen species formation
formyl-Met-Leu-Phe
H2O2
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Nox5 can be upregulated and activated by minute concentrations of hydrogen peroxide
heat shock protein 90
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binding of heat shock protein 90 to the C-terminus of Nox5 appears to stabilize the protein and enhance expression and activity
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interleukin-1beta
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stimulates Nox1
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ionomycin
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isoobtusilactone A
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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
latrunculin A
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enhancement of basal and hyperoxia-induced reactive oxygen species formation
N-formyl-L-methionyl-L-leucyl-L-phenylalanine
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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
NOXA1
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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
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NOXO1
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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
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p67phox
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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
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peptide C5a
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-
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phorbol 12-myristate 13-acetate
phorbol myristate acetate
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phosphate
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phosphatidylinositol 3-phosphate
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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-activating factor
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Poldip2
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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
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Protein kinase C
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-
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Rac
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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
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Rac1
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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
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salbutamol
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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
sodiumdodecylsulfate
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thrombin
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thyrotropin
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-
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TNF-alpha
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stimulates Nox1
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Trp-Lys-Tyr-Met-Val-Met
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activates
tumor necrosis factor-alpha
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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
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additional information
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