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PMID	17602948 ( )
Title	Nox enzymes, ROS, and chronic disease: an example of antagonistic pleiotropy.
Abstract	Reactive oxygen species (ROS) are considered to be chemically reactive with and damaging to biomolecules including DNA, protein, and lipid, and excessive exposure to ROS induces oxidative stress and causes genetic mutations. However, the recently described family of Nox and Duox enzymes generates ROS in a variety of tissues as part of normal physiological functions, which include innate immunity, signal transduction, and biochemical reactions, e.g., to produce thyroid hormone. Nature's "choice" of ROS to carry out these biological functions seems odd indeed, given its predisposition to cause molecular damage. This review describes normal biological roles of Nox enzymes as well as pathological conditions that are associated with ROS production by Nox enzymes. By far the most common conditions associated with Nox-derived ROS are chronic diseases that tend to appear late in life, including atherosclerosis, hypertension, diabetic nephropathy, lung fibrosis, cancer, Alzheimer's disease, and others. In almost all cases, with the exception of a few rare inherited conditions (e.g., related to innate immunity, gravity perception, and hypothyroidism), diseases are associated with overproduction of ROS by Nox enzymes; this results in oxidative stress that damages tissues over time. I propose that these pathological roles of Nox enzymes can be understood in terms of antagonistic pleiotropy: genes that confer a reproductive advantage early in life can have harmful effects late in life. Such genes are retained during evolution despite their harmful effects, because the force of natural selection declines with advanced age. This review discusses some of the proposed physiologic roles of Nox enzymes, and emphasizes the role of Nox enzymes in disease and the likely beneficial effects of drugs that target Nox enzymes, particularly in chronic diseases associated with an aging population. Laboratory Medicine, 615 Michael Street, Atlanta, GA 30322, USA. noxdoc@mac.com

NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.

Targets by SciMiner Summary

HUGO ID	Symbol	Target Name	#Occur	ActualStr
7889	NOX1	NADPH oxidase 1	55	Nox1-derived \| Mox1 \|
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	50	CGD \| Nox2 \| NOX2 \| gp91 phox \| Nox2-derived \|
7891	NOX4	NADPH oxidase 4	37	Nox4 \| NOX4 \|
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	15	angiotensinogen \| angiotensin ii \|
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	12	Nox5 \| nadph oxidase \|
7890	NOX3	NADPH oxidase 3	12	NOX3 \| Nox3 \|
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	11	chronic granulomatous disease \| p67 phox \|
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	8	p47 \| p47phox \|
2577	CYBA	cytochrome b-245, alpha polypeptide	8	p22 phox \|
4910	HIF1A	hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)	7	hif 1 \| HIF-1-dependent \| hypoxia inducible factor 1 \|
6871	MAPK1	mitogen-activated protein kinase 1	6	p40 \| MAPK \| p38 \|
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	6	nf kappa b \| NF-kappaB \|
6081	INS	insulin	5	insulin \|
7218	MPO	myeloperoxidase	5	myeloperoxidase \| MPO-deficient \|
6678	LPO	lactoperoxidase	5	LPO \| LPO-dependent \| lactoperoxidase \| LPO-mediated \|
3062	DUOX1	dual oxidase 1	4	Duox1 \|
13273	DUOX2	dual oxidase 2	4	DUOX2 \| Duox2 \|
7808	NGF	nerve growth factor (beta polypeptide)	4	NGF \| NGF-generated \|
19404	NOXO1	NADPH oxidase organizer 1	3	NOXO1 \|
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	3	Akt \| Rac-regulated \|
9393	PRKCA	protein kinase C, alpha	3	protein kinase c \|
5173	HRAS	v-Ha-ras Harvey rat sarcoma viral oncogene homolog	3	k ras \|
8799	PDGFA	platelet-derived growth factor alpha polypeptide	3	PDGF \|
3229	EGF	epidermal growth factor (beta-urogastrone)	2	EGF \|
6881	MAPK8	mitogen-activated protein kinase 8	2	JNK \|
11132	SNAP25	synaptosomal-associated protein, 25kDa	2	SNAP25 \| snap25 \|
6025	IL8	interleukin 8	2	IL-8 \| il 8 \|
9801	RAC1	ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)	2	Rac1 \|
12680	VEGFA	vascular endothelial growth factor A	2	VEGF \|
9395	PRKCB1	protein kinase C, beta 1	2	PKC-beta \| pkc beta \|
6877	MAPK3	mitogen-activated protein kinase 3	2	ERK1 \|
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	1	amyloid \|
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	1	nitric oxide synthase \|
9052	PLAU	plasminogen activator, urokinase	1	urokinase plasminogen activator \|
3415	EPO	erythropoietin	1	erythropoietin \|
11766	TGFB1	transforming growth factor, beta 1	1	TGF-beta1 \|
5344	ICAM1	intercellular adhesion molecule 1 (CD54), human rhinovirus receptor	1	ICAM-1 \|
4232	GDNF	glial cell derived neurotrophic factor	1	ATF-1 \|
8800	PDGFB	platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog)	1	platelet derived growth factor \|
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	1	activator protein 1 \|
10668	NOXA1	NADPH oxidase activator 1	1	NOXA1 \|
11517	TAC1	tachykinin, precursor 1	1	substance p \|
11764	TG	thyroglobulin	1	thyroglobulin \|
9958	REN	renin	1	renin \|
1516	CAT	catalase	1	catalase \|
1582	CCND1	cyclin D1	1	cyclin d1 \|
1071	BMP4	bone morphogenetic protein 4	1	BMP4 \|
9642	PTPN1	protein tyrosine phosphatase, non-receptor type 1	1	PTP1B \|
336	AGTR1	angiotensin II receptor, type 1	1	angiotensin ii receptor \|
6886	MAPK9	mitogen-activated protein kinase 9	1	jun kinase \|
12015	TPO	thyroid peroxidase	1	thyroid peroxidase \|
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	1	SOD1 \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
8799	PDGFA	platelet-derived growth factor alpha polypeptide	PDGF	1.2	disease PD Parkinson_amp_#x02019 s disease phox ph agocyte ox idase PDGF platelet-derived growth factor NOXO1 Nox organizer protein 1 NOXA1 Nox
19404	NOXO1	NADPH oxidase organizer 1	NOXO1	1.2	disease phox ph agocyte ox idase PDGF platelet-derived growth factor NOXO1 Nox organizer protein 1 NOXA1 Nox activator protein 1 FAD
10668	NOXA1	NADPH oxidase activator 1	NOXA1	1.5	idase PDGF platelet-derived growth factor NOXO1 Nox organizer protein 1 NOXA1 Nox activator protein 1 FAD flavin adenine dinucleotide NADPH nicotinamide
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	Such signaling targets include transcription factors such as NF-kappaB signaling proteins such as protein kinases and phosphatases and ion
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Nox2 and professional phagocytes The first role to be definitively established
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	express very large amounts of gp91 phox now also called Nox2 along with its regulatory subunits p47 phox p67 phox p40
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	1.2	phox now also called Nox2 along with its regulatory subunits p47 phox p67 phox p40 phox and Rac2 reviewed in 1
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	p67	0.3	also called Nox2 along with its regulatory subunits p47 phox p67 phox p40 phox and Rac2 reviewed in 1 2
6871	MAPK1	mitogen-activated protein kinase 1	p40	1.3	Nox2 along with its regulatory subunits p47 phox p67 phox p40 phox and Rac2 reviewed in 1 2
7218	MPO	myeloperoxidase	MPO	1.3	In addition myeloperoxidase (MPO) MPO is secreted into the phagosome where it converts H 2
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	where it converts H 2 O 2 (produced produced by Nox2 plus chloride into HOCl the latter has a direct microbicidal
7218	MPO	myeloperoxidase	MPO-deficient	1.0	has a direct microbicidal effect 4 5 (although although surprisingly MPO-deficient individuals do not suffer from markedly increased rates or apparent
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	CGD	2.5	is clear from the inherited condition chronic granulomatous disease (CGD) CGD that mutations resulting in defects in ROS generation by the
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	and other microbes 12 convincingly demonstrating a role for the Nox2 system in innate immunity mediated by professional phagocytes
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Nox2 and tissue inflammation Neutrophil-derived ROS including superoxide and H 2
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	ROS including superoxide and H 2 O 2 generated by Nox2 HONO generated from superoxide and nitric oxide and HOCl generated
7218	MPO	myeloperoxidase	MPO	1.3	generated from superoxide and nitric oxide and HOCl generated by MPO have been implicated in the tissue damage seen in acute
6678	LPO	lactoperoxidase	LPO	1.0	Nox enzymes and mucosal immunity Lactoperoxidase (LPO) LPO catalyzes the H 2 O 2 -dependent oxidation of the
13273	DUOX2	dual oxidase 2	Duox2	0.9	Epithelial cells in salivary ducts express Duox2 and those in trachea and bronchus express Duox1 these Duox
3062	DUOX1	dual oxidase 1	Duox1	0.9	ducts express Duox2 and those in trachea and bronchus express Duox1 these Duox enzymes are likely to play a role in
6678	LPO	lactoperoxidase	LPO-dependent	1.0	humans as a source of H 2 O 2 for LPO-dependent antimicrobial activity 22
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Induction of Nox1 and other mucosal Nox enzymes by cytokines 23 and bacterial
7889	NOX1	NADPH oxidase 1	Nox1	3.7	mucosal innate immunity although it should also be noted that Nox1 is induced by a variety of other agonists including growth
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	1.2	of 45 polymorphisms in ten Nox/ROS-related Nox ROS-related genes including p47 phox p67 phox p40 phox p22 phox gp91 phox Duox1
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	p67	0.3	polymorphisms in ten Nox/ROS-related Nox ROS-related genes including p47 phox p67 phox p40 phox p22 phox gp91 phox Duox1 and Duox2
6871	MAPK1	mitogen-activated protein kinase 1	p40	1.3	ten Nox/ROS-related Nox ROS-related genes including p47 phox p67 phox p40 phox p22 phox gp91 phox Duox1 and Duox2 in a
3062	DUOX1	dual oxidase 1	Duox1	0.9	p47 phox p67 phox p40 phox p22 phox gp91 phox Duox1 and Duox2 in a cohort of 95 lung disease individuals
13273	DUOX2	dual oxidase 2	DUOX2	0.9	p47 phox p67 phox p40 phox p22 phox gp91 phox Duox1 and Duox2 in a cohort of 95 lung disease individuals
13273	DUOX2	dual oxidase 2	Duox2	0.9	p67 phox p40 phox p22 phox gp91 phox Duox1 and Duox2 in a cohort of 95 lung disease individuals and 95
2577	CYBA	cytochrome b-245, alpha polypeptide	p22	0.0	Nox ROS-related genes including p47 phox p67 phox p40 phox p22 phox gp91 phox Duox1 and Duox2 in a cohort of
3062	DUOX1	dual oxidase 1	Duox1	0.9	mechanisms Microbial defense In addition to the role of Duox1/2 Duox1 2 in LPO-mediated immunity described above ROS produced by Nox(es)
6678	LPO	lactoperoxidase	LPO-mediated	1.0	In addition to the role of Duox1/2 Duox1 2 in LPO-mediated immunity described above ROS produced by Nox(es) Nox es plays
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	1.2	NADPH-oxidase components p47 phox p67 phox and Nox4 (but but not Nox2 were
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	p67	0.3	NADPH-oxidase components p47 phox p67 phox and Nox4 (but but not Nox2 were expressed in
7891	NOX4	NADPH oxidase 4	Nox4	0.9	NADPH-oxidase components p47 phox p67 phox and Nox4 (but but not Nox2 were expressed in lung fibroblasts and
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	components p47 phox p67 phox and Nox4 (but but not Nox2 were expressed in lung fibroblasts and p67 phox was induced
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	p67	0.3	(but but not Nox2 were expressed in lung fibroblasts and p67 phox was induced by rhinovirus accompanied by increased ROS and
6025	IL8	interleukin 8	IL-8	1.3	induced by rhinovirus accompanied by increased ROS and elaboration of IL-8 27
4910	HIF1A	hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)	HIF-1	1.2	related signaling events including activation of hypoxia-inducible factor 1 (HIF-1) HIF-1 represent important features of lung cell physiology and lung function
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Up-regulation of Nox1 mRNA and protein occurred during hypoxia accompanied by enhanced reactive
4910	HIF1A	hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)	HIF-1-dependent	1.7	(ROS) ROS generation the latter was accompanied by activation of HIF-1-dependent gene expression which was blocked by catalase
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Thus hypoxic upregulation of Nox1 and subsequently augmented ROS generation may activate HIF-1-dependent pathways and
4910	HIF1A	hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)	HIF-1-dependent	1.7	upregulation of Nox1 and subsequently augmented ROS generation may activate HIF-1-dependent pathways and participate in adaptation to high altitude 40
6678	LPO	lactoperoxidase	LPO	1.0	fibroblasts which in the presence of heme-type peroxidases such as LPO and MPO can mediate oxidative cross-linking of tyrosine residues in
7218	MPO	myeloperoxidase	MPO	1.3	in the presence of heme-type peroxidases such as LPO and MPO can mediate oxidative cross-linking of tyrosine residues in extracellular matrix
6881	MAPK8	mitogen-activated protein kinase 8	JNK	0.3	ROS produced in lung epithelial cells activated JNK and caused cell death via TNF-RI and the TRAF2-ASK1 signaling
19404	NOXO1	NADPH oxidase organizer 1	NOXO1	1.2	Cigarette smoke and the bacterial product LPS both up-regulate NOXO1 the activator of Nox1 31
7889	NOX1	NADPH oxidase 1	Nox1	3.7	the bacterial product LPS both up-regulate NOXO1 the activator of Nox1 31
7890	NOX3	NADPH oxidase 3	Nox3	0.9	TLR4 deficiency which causes emphysema in mice up-regulated Nox3 in lung and endothelial cells resulting in increased oxidant generation
7890	NOX3	NADPH oxidase 3	Nox3	0.9	_amp_#x02212 mice or endothelial cells with chemical Nox inhibitors or Nox3 siRNA prevented the disease development 32
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	In addition to the Nox2 system which is highly expressed in inflammatory cells including the
7891	NOX4	NADPH oxidase 4	Nox4	0.9	asthmatic lung airway smooth muscle cells express Nox enzymes particularly Nox4 which have been proposed to contribute to tissue destruction in
7891	NOX4	NADPH oxidase 4	Nox4	0.9	is implicated in pulmonary hypertension potently induced p22 phox and Nox4 in lung smooth muscle markedly increasing ROS levels that activate
6877	MAPK3	mitogen-activated protein kinase 3	ERK1	1.3	in lung smooth muscle markedly increasing ROS levels that activate ERK1 2 p38 MAPK Jun Kinase and Akt
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.1	smooth muscle markedly increasing ROS levels that activate ERK1 2 p38 MAPK Jun Kinase and Akt
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	1.6	muscle markedly increasing ROS levels that activate ERK1 2 p38 MAPK Jun Kinase and Akt
2577	CYBA	cytochrome b-245, alpha polypeptide	p22	0.0	urotensin II which is implicated in pulmonary hypertension potently induced p22 phox and Nox4 in lung smooth muscle markedly increasing ROS
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	Akt	0.0	levels that activate ERK1 2 p38 MAPK Jun Kinase and Akt
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Nox2 and Nox4 are both expressed in endothelium 41 42 where
7891	NOX4	NADPH oxidase 4	NOX4	0.9	Nox2 and Nox4 are both expressed in endothelium 41 42 where
7891	NOX4	NADPH oxidase 4	Nox4	0.9	Nox2 and Nox4 are both expressed in endothelium 41 42 where under some
7889	NOX1	NADPH oxidase 1	Nox1	3.7	under some conditions they participate in cell proliferation 43 while Nox1 Nox4 42 44 and Nox2 45 are expressed in vascular
7891	NOX4	NADPH oxidase 4	Nox4	0.9	some conditions they participate in cell proliferation 43 while Nox1 Nox4 42 44 and Nox2 45 are expressed in vascular smooth
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	in cell proliferation 43 while Nox1 Nox4 42 44 and Nox2 45 are expressed in vascular smooth muscle cells
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Nox1 in vascular smooth muscle participates in cell proliferation 46 while
7891	NOX4	NADPH oxidase 4	Nox4	0.9	in vascular smooth muscle participates in cell proliferation 46 while Nox4 in these cells participates in maintenance of the differentiated phenotype
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Nox2 and associated regulatory proteins are also expressed in adventitia where
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	Nox5	0.9	In addition Nox5 is expressed in vascular smooth muscle 51 and Petumnetcha and
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Nox enzymes in the myocardium Both Nox2 and Nox4 are expressed in cardiomyocytes
7891	NOX4	NADPH oxidase 4	NOX4	0.9	Nox enzymes in the myocardium Both Nox2 and Nox4 are expressed in cardiomyocytes
7891	NOX4	NADPH oxidase 4	Nox4	0.9	Nox enzymes in the myocardium Both Nox2 and Nox4 are expressed in cardiomyocytes
7891	NOX4	NADPH oxidase 4	Nox4	0.9	Nox4 is necessary for the differentiation of mouse embryonic stem cells
7891	NOX4	NADPH oxidase 4	Nox4	0.9	In addition Nox4 may contribute to the pathological activation of cardiac fibroblasts in
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	ventricular hypertrophy (LVH), LVH and this correlated with overexpression of Nox2 in Angiotensin II-induced LVH and in pressure overload LVH with
7891	NOX4	NADPH oxidase 4	Nox4	0.9	Angiotensin II-induced LVH and in pressure overload LVH with both Nox4 55 and Nox2 56
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	and in pressure overload LVH with both Nox4 55 and Nox2 56
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Nox2 overexpression in cardiomyocytes is seen following myocardial infarction 58 and
7889	NOX1	NADPH oxidase 1	Nox1	3.7	levels of cytokines which are associated with increased levels of Nox1 Nox2 and Nox4 59
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	of cytokines which are associated with increased levels of Nox1 Nox2 and Nox4 59
7891	NOX4	NADPH oxidase 4	NOX4	0.9	of cytokines which are associated with increased levels of Nox1 Nox2 and Nox4 59
7891	NOX4	NADPH oxidase 4	Nox4	0.9	which are associated with increased levels of Nox1 Nox2 and Nox4 59
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Myocardial Nox2 also contributes to superoxide production in the fibrillating human atrial
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.1	smooth muscle cells regulate the activity of the signaling proteins p38 MAPK and Akt 42 and are essential for Angiotensin II-induced
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	1.6	muscle cells regulate the activity of the signaling proteins p38 MAPK and Akt 42 and are essential for Angiotensin II-induced calcium
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	Akt	0.1	regulate the activity of the signaling proteins p38 MAPK and Akt 42 and are essential for Angiotensin II-induced calcium fluxes (Petumnetcha
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Nox1 in the vasculature plays a central role in hypertension
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Nox enzymes (particularly particularly Nox1 and ROS are induced in vascular cells by growth stimuli
8799	PDGFA	platelet-derived growth factor alpha polypeptide	PDGF	1.2	are induced in vascular cells by growth stimuli Angiotensin II PDGF lyso-phosphatidylcholine thrombin 42 44 64 urokinase plasminogen activator 65 by
4232	GDNF	glial cell derived neurotrophic factor	ATF-1	0.9	42 44 64 urokinase plasminogen activator 65 by PGF2_amp_#x003b1 and ATF-1 66 and by inflammatory stimuli e.g. TNF_amp_#x003b1 and IL1_amp_#x003b2 67
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Nox1 was also markedly overexpressed in transgenic hypertensive rats overexpressing the
7889	NOX1	NADPH oxidase 1	Nox1	3.7	In the latter animals overexpression of Nox1 and to a lesser extent Nox4 was dependent upon Angiotensin
7891	NOX4	NADPH oxidase 4	Nox4	0.9	latter animals overexpression of Nox1 and to a lesser extent Nox4 was dependent upon Angiotensin II type 1 receptors
7889	NOX1	NADPH oxidase 1	Nox1	3.7	-induced hypertrophy of smooth muscle cells is associated with elevated Nox1 and reduction of Nox1 using ribozymes protected against hypertrophy 69
7889	NOX1	NADPH oxidase 1	Nox1	3.7	muscle cells is associated with elevated Nox1 and reduction of Nox1 using ribozymes protected against hypertrophy 69
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Decreased expression of Nox1 in vascular smooth muscle cells using antisense RNA also resulted
7889	NOX1	NADPH oxidase 1	Nox1	3.7	In mice overexpression in vascular smooth muscle of Nox1 70 or of p22 phox 71 (which which indirectly increases
7889	NOX1	NADPH oxidase 1	Nox1	3.7	70 or of p22 phox 71 (which which indirectly increases Nox1 expression 72 resulted in a marked increase in systolic blood
2577	CYBA	cytochrome b-245, alpha polypeptide	p22	0.0	overexpression in vascular smooth muscle of Nox1 70 or of p22 phox 71 (which which indirectly increases Nox1 expression 72 resulted
7889	NOX1	NADPH oxidase 1	Nox1	3.7	In Nox1 knockout mice there was a lowering of basal blood pressure
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Nox2 has also been implicated in some models of hypertension
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Nox2 accounts for significant ROS generation in vascular smooth muscle in
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2-derived	2.5	In a model of renovascular hypertension Nox2-derived superoxide decreased NO bioavailability and there was marked protection from
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	bioavailability and there was marked protection from hypertension in the Nox2 (_amp_#x02212;/_amp_#x02212;) _amp_#x02212 _amp_#x02212 mice 61
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	In low renin salt-sensitive hypertension a tat-peptide inhibitor of Nox2 normalized ROS generation and endothelium-dependent vascular relaxation 77
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Nox1 and Nox2 therefore provide promising targets for therapeutic intervention in
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	NOX2	2.8	Nox1 and Nox2 therefore provide promising targets for therapeutic intervention in
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Nox1 and Nox2 therefore provide promising targets for therapeutic intervention in hypertensive cardiovascular
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Human atherosclerotic plaques express large amounts of Nox2 77 which was localized to the plaque shoulder an area
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	the ROS in atherosclerotic plaques arises from Nox enzymes particularly Nox2
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Oscillatory sheer stress results in several-fold induction of Nox1 Nox2 and Nox4 in vascular endothelium (with with opposite effects
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Oscillatory sheer stress results in several-fold induction of Nox1 Nox2 and Nox4 in vascular endothelium (with with opposite effects of
7891	NOX4	NADPH oxidase 4	NOX4	0.9	Oscillatory sheer stress results in several-fold induction of Nox1 Nox2 and Nox4 in vascular endothelium (with with opposite effects of
7891	NOX4	NADPH oxidase 4	Nox4	0.9	sheer stress results in several-fold induction of Nox1 Nox2 and Nox4 in vascular endothelium (with with opposite effects of the anti-atherogenic
1071	BMP4	bone morphogenetic protein 4	BMP4	0.3	is associated with induction of bone morphogenic protein 4 (BMP4) BMP4 82 which induces Nox1 and p47phox resulting in an oxidative
7889	NOX1	NADPH oxidase 1	Nox1	3.7	of bone morphogenic protein 4 (BMP4) BMP4 82 which induces Nox1 and p47phox resulting in an oxidative stress that leads to
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47phox	1.3	morphogenic protein 4 (BMP4) BMP4 82 which induces Nox1 and p47phox resulting in an oxidative stress that leads to ICAM-1 expression
5344	ICAM1	intercellular adhesion molecule 1 (CD54), human rhinovirus receptor	ICAM-1	0.6	and p47phox resulting in an oxidative stress that leads to ICAM-1 expression and monocyte adhesion 81
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Nox1 expression increases ~3-fold following balloon injury and precedes re-stenosis and
12680	VEGFA	vascular endothelial growth factor A	VEGF	2.2	vascular remodeling seen in atherosclerosis 86 87 and induction of VEGF 88 89 which contributes to the growth of new microvessels
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Therefore inhibition of Nox2 and/or and or Nox1 is likely to be useful for
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Therefore inhibition of Nox2 and/or and or Nox1 is likely to be useful for the prevention and treatment
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Nox enzymes particularly the Rac-regulated enzymes Nox1 and Nox2 play a role in endothelial dysfunction in the
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	NOX2	2.8	Nox enzymes particularly the Rac-regulated enzymes Nox1 and Nox2 play a role in endothelial dysfunction in the
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Nox enzymes particularly the Rac-regulated enzymes Nox1 and Nox2 play a role in endothelial dysfunction in the setting of
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	Rac-regulated	0.1	Nox enzymes particularly the Rac-regulated enzymes Nox1 and Nox2 play a role in endothelial dysfunction
9801	RAC1	ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)	Rac1	0.0	Consistent with a role for these Nox isoforms dominant negative Rac1 protected against oxidative stress and endothelial dysfunction in a mouse
9801	RAC1	ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)	Rac1	0.0	Indeed impaired activation of Rac1 and Nox-dependent oxidative stress has been proposed to underlie some
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	ROS production via a protein kinase C-dependent mechanism resulting in NF-kappaB activation and induction of inflammatory genes 98
7891	NOX4	NADPH oxidase 4	Nox4	0.9	Renal Nox enzymes Nox4 is expressed in high levels in kidney 99 100 while
7889	NOX1	NADPH oxidase 1	Nox1	3.7	expressed in high levels in kidney 99 100 while other Nox1 Nox2 and Nox regulatory subunits are expressed at lower but
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	in high levels in kidney 99 100 while other Nox1 Nox2 and Nox regulatory subunits are expressed at lower but quantitatively
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Apocyanin an inhibitor of Nox2 and probably other Nox enzymes was used in rat to
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Kidneys of rats with diabetes mellitus had increased expression of Nox2 p47 phox and Nox4 101 109 increased membrane translocation of
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	1.2	of rats with diabetes mellitus had increased expression of Nox2 p47 phox and Nox4 101 109 increased membrane translocation of p47
7891	NOX4	NADPH oxidase 4	Nox4	0.9	diabetes mellitus had increased expression of Nox2 p47 phox and Nox4 101 109 increased membrane translocation of p47 phox (reflecting reflecting
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	1.2	p47 phox and Nox4 101 109 increased membrane translocation of p47 phox (reflecting reflecting Nox2 activation 101 and increased mesangial matrix
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	101 109 increased membrane translocation of p47 phox (reflecting reflecting Nox2 activation 101 and increased mesangial matrix 101
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	protein in diabetic rats prevented the increased renal expression of Nox2 and membrane translocation of p47 phox and blocked the mesangial
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	1.2	the increased renal expression of Nox2 and membrane translocation of p47 phox and blocked the mesangial matrix expansion 101
11766	TGFB1	transforming growth factor, beta 1	TGF-beta1	0.3	included inhibition of Na /glucose glucose co-transport increased secretion of TGF-beta1 and activation of NF-kappaB signaling 110
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	/glucose glucose co-transport increased secretion of TGF-beta1 and activation of NF-kappaB signaling 110
9395	PRKCB1	protein kinase C, beta 1	PKC-beta	2.2	PKC-beta (_amp_#x02212;/_amp_#x02212;) _amp_#x02212 _amp_#x02212 diabetic mice were protected against induction of
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	(_amp_#x02212;/_amp_#x02212;) _amp_#x02212 _amp_#x02212 diabetic mice were protected against induction of Nox2 Nox4 and glucose-induced renal dysfunction and fibrosis indicating a role
7891	NOX4	NADPH oxidase 4	Nox4	0.9	_amp_#x02212 _amp_#x02212 diabetic mice were protected against induction of Nox2 Nox4 and glucose-induced renal dysfunction and fibrosis indicating a role for
7891	NOX4	NADPH oxidase 4	Nox4	0.9	Nox4 is a major source of ROS in diabetic nephropathy based
7891	NOX4	NADPH oxidase 4	Nox4	0.9	ROS generation and fibronectin expression in kidney cells transfected with Nox4 antisense oligonucleotides 111
7891	NOX4	NADPH oxidase 4	Nox4	0.9	Thus drugs targeting Nox4 and possibly Nox2 appear to be promising for the treatment
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Thus drugs targeting Nox4 and possibly Nox2 appear to be promising for the treatment and prevention of
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	chronically with aldosterone and salt is associated with induction of Nox2 Nox4 and p22 phox 114 increased p47 phox and p67
7891	NOX4	NADPH oxidase 4	Nox4	0.9	with aldosterone and salt is associated with induction of Nox2 Nox4 and p22 phox 114 increased p47 phox and p67 phox
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	1.2	with induction of Nox2 Nox4 and p22 phox 114 increased p47 phox and p67 phox in the membrane fraction (indicating indicating
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	p67	0.3	Nox2 Nox4 and p22 phox 114 increased p47 phox and p67 phox in the membrane fraction (indicating indicating activation of the
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	phox in the membrane fraction (indicating indicating activation of the Nox2 system and increased renal ROS and 102
2577	CYBA	cytochrome b-245, alpha polypeptide	p22	0.1	and salt is associated with induction of Nox2 Nox4 and p22 phox 114 increased p47 phox and p67 phox in the
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	In an Angiotensin II-induced mesangioproliferative model of glomerulonephritis Nox2 and Nox4 induction were associated with disease progression and treatment
7891	NOX4	NADPH oxidase 4	NOX4	0.9	In an Angiotensin II-induced mesangioproliferative model of glomerulonephritis Nox2 and Nox4 induction were associated with disease progression and treatment
7891	NOX4	NADPH oxidase 4	Nox4	0.9	In an Angiotensin II-induced mesangioproliferative model of glomerulonephritis Nox2 and Nox4 induction were associated with disease progression and treatment with the
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Angiotensin II-infused rodents show increased renal and systemic expression of Nox1 117 which contributes to the development and maintenance of hypertension
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Genetically salt-sensitive rats show a 3-fold higher expression of renal Nox1 compared with control rats and overexpression was associated with increased
6877	MAPK3	mitogen-activated protein kinase 3	ERK1	1.3	control rats and overexpression was associated with increased activity of ERK1 2 and JNK kinases 118
6881	MAPK8	mitogen-activated protein kinase 8	JNK	0.3	overexpression was associated with increased activity of ERK1 2 and JNK kinases 118
7891	NOX4	NADPH oxidase 4	Nox4	0.9	of this ROS is Nox enzymes this includes melanoma (Nox4, Nox4 127 prostate cancer (Nox5 Nox5 128 and Nox1 129 glioblastoma
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	Nox5	0.9	enzymes this includes melanoma (Nox4, Nox4 127 prostate cancer (Nox5 Nox5 128 and Nox1 129 glioblastoma (Nox4 Nox4 and sometimes Nox5
7889	NOX1	NADPH oxidase 1	Nox1	3.7	melanoma (Nox4, Nox4 127 prostate cancer (Nox5 Nox5 128 and Nox1 129 glioblastoma (Nox4 Nox4 and sometimes Nox5 130 H pylorus
7891	NOX4	NADPH oxidase 4	Nox4	0.9	prostate cancer (Nox5 Nox5 128 and Nox1 129 glioblastoma (Nox4 Nox4 and sometimes Nox5 130 H pylorus -induced gastric inflammation leading
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	Nox5	0.9	Nox5 128 and Nox1 129 glioblastoma (Nox4 Nox4 and sometimes Nox5 130 H pylorus -induced gastric inflammation leading to gastric cancer
7889	NOX1	NADPH oxidase 1	Nox1	3.7	H pylorus -induced gastric inflammation leading to gastric cancer (Nox1 Nox1 131 and Barrett_amp_#x02019 s esophageal adenocarcinoma (Nox5 Nox5 132
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	Nox5	0.9	cancer (Nox1 Nox1 131 and Barrett_amp_#x02019 s esophageal adenocarcinoma (Nox5 Nox5 132
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Some but not all reports have observed an increase in Nox1 expression in colon cancer see 133 _amp_#x02013 136
7889	NOX1	NADPH oxidase 1	Nox1	3.7	In recent studies we found that Nox1 protein and mRNA are over-expressed beginning at the adenoma (precancerous
7889	NOX1	NADPH oxidase 1	Nox1	3.7	strong correlation with oncogenic mutations in K-Ras and markedly elevated Nox1 levels in the intestinal tract were also seen in mice
7889	NOX1	NADPH oxidase 1	Nox1	3.7	model epithelial cell line that showed a marked induction of Nox1 mRNA and ROS 137
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Decreasing the expression of Nox1 (originally originally called Mox1 decreased cell division in vascular smooth
7889	NOX1	NADPH oxidase 1	Mox1	1.9	Decreasing the expression of Nox1 (originally originally called Mox1 decreased cell division in vascular smooth muscle 46 and in
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	Nox5	0.9	Suppression of Nox5 expression in Barrett_amp_#x02019 s esophageal adenocarcinoma cells likewise inhibited proliferation
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Proliferating keratinocytes showed higher ROS generation and Nox1 levels than quiescent cells 123
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Over-expression of Nox1 in several cell types is associated with increased cell division
7889	NOX1	NADPH oxidase 1	Nox1	3.7	In fibroblasts that over-expressed heterologous Nox1 and also harbored an oncogenic mutation in Ras overexpression of
7889	NOX1	NADPH oxidase 1	Nox1	3.7	In actively cycling cells Nox1 stimulated proliferation by reducing the requirement for growth factors to
7889	NOX1	NADPH oxidase 1	Nox1	3.7	maintain expression of cyclin D1 whereas during cell cycle re-entry Nox1 activity was required for transcriptional activation of Fos family genes
7889	NOX1	NADPH oxidase 1	Nox1	3.7	and angiogenesis In studies in prostate tumor cells that over-expressed Nox1 Nox1-derived H 2 O 2 had only a small effect
7889	NOX1	NADPH oxidase 1	Nox1-derived	1.9	angiogenesis In studies in prostate tumor cells that over-expressed Nox1 Nox1-derived H 2 O 2 had only a small effect on
7889	NOX1	NADPH oxidase 1	Nox1	3.7	However in animals Nox1 over-expression markedly increased angiogenesis by inducing the angiogenic factor VEGF
12680	VEGFA	vascular endothelial growth factor A	VEGF	2.2	Nox1 over-expression markedly increased angiogenesis by inducing the angiogenic factor VEGF 89 correlating with an aggressive tumor phenotype
7889	NOX1	NADPH oxidase 1	Nox1	3.7	A similar role for Nox1 in angiogenesis in atherosclerosis has been proposed 88
7891	NOX4	NADPH oxidase 4	Nox4	0.9	to the frequently reported pro-apoptotic effect of ROS ROS from Nox4 in pancreatic cells 141 and from Nox1 in colon adenoma
7889	NOX1	NADPH oxidase 1	Nox1	3.7	ROS ROS from Nox4 in pancreatic cells 141 and from Nox1 in colon adenoma and carcinoma 136 inhibit apoptosis
7891	NOX4	NADPH oxidase 4	Nox4	0.9	In pancreatic cancer cells depletion of Nox4 or ROS triggered apopotosis 142 predicting a therapeutic effect of
7889	NOX1	NADPH oxidase 1	Nox1	3.7	In colon carcinoma cells Nox1 controls the expression of specific integrins at the cell surface
3229	EGF	epidermal growth factor (beta-urogastrone)	EGF	0.3	In A431 carcinoma cells the growth factor EGF activates Nox-dependent ROS generation and this in turn regulates expression
7891	NOX4	NADPH oxidase 4	Nox4	0.9	In pancreatic cancer cells ECM stimulated ROS production through Nox4 resulting in increased cell survival 147
7808	NGF	nerve growth factor (beta polypeptide)	NGF	0.6	NGF stimulates ROS generation in PC12 cells in a Rac1-dependent manner
7808	NGF	nerve growth factor (beta polypeptide)	NGF-generated	0.6	ROS generation in PC12 cells in a Rac1-dependent manner and NGF-generated ROS participates in neuronal differentiation 148
7808	NGF	nerve growth factor (beta polypeptide)	NGF	0.6	ROS in neurons also enhances voltage-gated K currents elicited by NGF mediated by activation of NF-kappaB 149
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	voltage-gated K currents elicited by NGF mediated by activation of NF-kappaB 149
11132	SNAP25	synaptosomal-associated protein, 25kDa	SNAP25	0.8	A possible target is the fusion protein SNAP25 which may function as a presynaptic ROS sensor 155
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Nox2 is expressed in relatively high levels in microglia 156 the
7891	NOX4	NADPH oxidase 4	Nox4	0.9	Nox4 is expressed in neurons and capillaries of the brain and
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Neuronal Nox1 is induced in response to NGF and suppresses neurite outgrowth
7808	NGF	nerve growth factor (beta polypeptide)	NGF	0.6	Neuronal Nox1 is induced in response to NGF and suppresses neurite outgrowth 159
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	Nox5	0.9	Nox5 shows significant expression in cerebrum and Duox1 is highly expressed
3062	DUOX1	dual oxidase 1	Duox1	0.9	Nox5 shows significant expression in cerebrum and Duox1 is highly expressed in cerebellum (Cheng Cheng and Lambeth unpublished
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Remarkably Nox1 knockout mice show a marked change in their ability to
7889	NOX1	NADPH oxidase 1	Nox1	3.7	This suggests that drugs inhibiting Nox1 activity could find applications in inflammatory pain control
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.5	s Disease (AD) AD are extracellular deposits of fibrillar _amp_#x003b2 -amyloid protein (plaques) plaques and neuronal loss resulting in progressive cognitive
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	direct oxidative damage or by over-activating death-promoting signaling systems including NF-kappaB 163
7889	NOX1	NADPH oxidase 1	Nox1	3.7	168 _amp_#x02013 170 although there is also increased expression of Nox1 and Nox3 in AD brain 164
7890	NOX3	NADPH oxidase 3	NOX3	0.9	168 _amp_#x02013 170 although there is also increased expression of Nox1 and Nox3 in AD brain 164
7890	NOX3	NADPH oxidase 3	Nox3	0.9	170 although there is also increased expression of Nox1 and Nox3 in AD brain 164
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	in increased ROS by inhibiting mitochondrial respiration and by activating Nox2 in microglia 171
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	activates the microglial inflammatory response releasing proinflammatory factors activating glial Nox2 and producing neuronal loss 175 176
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	In this model of Parkinson_amp_#x02019 s Disease Nox2 knockout mice were significantly protected against loss of nigral dopaminergic
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	substance P produced in substantia nigra can also activate glial Nox2 and could play a role in PD 177
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	0.8	assumed to be due to decreased oxidative defense mechanisms because SOD1 is mutated in familial forms of the disease 179
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Recently the Nox2 system was found to be activated in the spinal cord
7890	NOX3	NADPH oxidase 3	Nox3	0.9	Nox3 and Inner Ear Function
7890	NOX3	NADPH oxidase 3	Nox3	0.9	Nox3 and Inner Ear Function a
7890	NOX3	NADPH oxidase 3	Nox3	0.9	Nox3 and gravity perception The highest expression of Nox3 is in
7890	NOX3	NADPH oxidase 3	Nox3	0.9	Nox3 and gravity perception The highest expression of Nox3 is in the inner ear specifically in vestibular and cochlear
7890	NOX3	NADPH oxidase 3	Nox3	0.9	Several of these mouse strains showed mutations in either Nox3 183 or its regulatory subunit NOXO1 184
19404	NOXO1	NADPH oxidase organizer 1	NOXO1	1.2	showed mutations in either Nox3 183 or its regulatory subunit NOXO1 184
7890	NOX3	NADPH oxidase 3	Nox3	0.9	Nox3 and Inner Ear Function b
7890	NOX3	NADPH oxidase 3	Nox3	0.9	Nox3 ototoxicity and deafness Deafness and the ototoxicity of certain drugs
7890	NOX3	NADPH oxidase 3	Nox3	0.9	Nox3 in the inner ear is induced by cisplatin suggesting that
13273	DUOX2	dual oxidase 2	Duox2	0.9	The essential role for Duox2 in thyroid hormone biosynthesis is demonstrated conclusively by the occurrence
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Pancreatic islets diabetes and Nox enzymes Nox1 Nox2 and Nox4 were found in pancreatic islet cells and
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	2.8	Pancreatic islets diabetes and Nox enzymes Nox1 Nox2 and Nox4 were found in pancreatic islet cells and glucose-stimulated
7891	NOX4	NADPH oxidase 4	NOX4	0.9	Pancreatic islets diabetes and Nox enzymes Nox1 Nox2 and Nox4 were found in pancreatic islet cells and glucose-stimulated
7891	NOX4	NADPH oxidase 4	Nox4	0.9	Pancreatic islets diabetes and Nox enzymes Nox1 Nox2 and Nox4 were found in pancreatic islet cells and glucose-stimulated insulin secretion
7889	NOX1	NADPH oxidase 1	Nox1	3.7	In type II diabetes increased expression of Nox1 occurs in islets and may exacerbate disease over time by
7889	NOX1	NADPH oxidase 1	Nox1	3.7	In a model of pancreatitis Nox1 and/or and or other Nox enzymes were implicated in the
7889	NOX1	NADPH oxidase 1	Nox1	3.7	Signaling role of Nox enzymes in hormonal responses Nox1 induction and activation is implicated in the hormonal response to
8799	PDGFA	platelet-derived growth factor alpha polypeptide	PDGF	1.2	hormonal response to Angiotensin II and growth factors such as PDGF and EGF ( vide infra
3229	EGF	epidermal growth factor (beta-urogastrone)	EGF	0.3	to Angiotensin II and growth factors such as PDGF and EGF ( vide infra
7891	NOX4	NADPH oxidase 4	Nox4	0.9	In addition recent studies implicate Nox4 in the tissue response to insulin 198 199
9642	PTPN1	protein tyrosine phosphatase, non-receptor type 1	PTP1B	2.8	in part by ROS inhibition of the protein tyrosine phosphatase PTP1B
7891	NOX4	NADPH oxidase 4	Nox4	0.9	Nox4 in osteoclasts may be the source of the ROS in
7891	NOX4	NADPH oxidase 4	Nox4	0.9	In chondrocyte cell lines Nox4 is implicated as the source of the interleukin 1_amp_#x003b2 -dependent
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	Nox5	0.9	surprising observation that knocking down the expression of the Drosophila Nox5 with si-RNA resulted in female sterility
7889	NOX1	NADPH oxidase 1	Nox1	3.7	likewise dependent upon the generation of a Nox (probably probably Nox1 -generated H 2 O 2 signal
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	activator protein 1	1.0	ros reactive oxygen species ad alzheimer_amp_#x02019;s disease pd parkinson_amp_#x02019;s disease phox ph agocyte ox idase pdgf platelet derived growth factor noxo1 nox organizer protein 1 noxa1 nox activator protein 1 fad flavin adenine dinucleotide nadph nicotinamide adenine dinucleotide phosphate reduced form
8800	PDGFB	platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog)	platelet derived growth factor	1.0	nox nadph oxidase duox dual oxidase ros reactive oxygen species ad alzheimer_amp_#x02019;s disease pd parkinson_amp_#x02019;s disease phox ph agocyte ox idase pdgf platelet derived growth factor noxo1 nox organizer protein 1 noxa1 nox activator protein 1 fad flavin adenine dinucleotide nadph nicotinamide adenine dinucleotide phosphate reduced form
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	nadph oxidase	1.0	nox nadph oxidase duox dual oxidase ros reactive oxygen species ad alzheimer_amp_#x02019;s disease pd parkinson_amp_#x02019;s disease phox ph agocyte ox idase pdgf platelet derived growth factor noxo1 nox organizer pr
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	p67 phox	1.0	these cells express very large amounts of gp91 phox now also called nox2 along with its regulatory subunits p47 phox p67 phox p40 phox and rac2 reviewed in [ 1 2 ].
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	gp91 phox	1.0	these cells express very large amounts of gp91 phox now also called nox2 along with its regulatory subunits p47 phox p67 phox p40 phox and rac2 reviewed in [ 1 2 ].
7218	MPO	myeloperoxidase	myeloperoxidase	1.0	in addition myeloperoxidase mpo is secreted into the phagosome where it converts h 2 o 2 produced by nox2 plus chloride into hocl; the latter has a direct microbicidal effect [ 4 5 ] although surprisingly mpo deficient individu
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	nadph oxidase	1.0	the activity of the phagocyte nadph oxidase also triggers opening of proton [ 8 _amp_#x02013; 11 ] and possibly potassium channels [ 3 ] that are proposed to change the ionic environment of the phagosome thereby activating microbicidal proteas
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	chronic granulomatous disease	1.0	regardless of the precise mechanisms it is clear from the inherited condition chronic granulomatous disease cgd that mutations resulting in defects in ros generation by the respiratory burst oxidase are associated with an inability of phagocytes to kill bacteria and other microbes [ 12 ] convincingly demon
6678	LPO	lactoperoxidase	lactoperoxidase	1.0	nox enzymes and mucosal immunity lactoperoxidase lpo catalyzes the h 2 o 2 dependent oxidation of the anion thiocyanate to form the antimicrobial compound hoscn that prevents growth of bacteria fungi and viruses [ 20 21 ] but the origin of the h 2
2577	CYBA	cytochrome b-245, alpha polypeptide	p22 phox	1.0	examination of 45 polymorphisms in ten nox/ros related genes including p47 phox p67 phox p40 phox p22 phox gp91 phox duox1 and duox2 in a cohort of 95 lung disease individuals and 95 control individuals did not show an association of these polymorphisms with increased susceptibility to infectious or infla
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	p67 phox	1.0	examination of 45 polymorphisms in ten nox/ros related genes including p47 phox p67 phox p40 phox p22 phox gp91 phox duox1 and duox2 in a cohort of 95 lung disease individuals and 95 control individuals did not show an association of these polymorphisms with increased susceptibility to i
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	gp91 phox	1.0	examination of 45 polymorphisms in ten nox/ros related genes including p47 phox p67 phox p40 phox p22 phox gp91 phox duox1 and duox2 in a cohort of 95 lung disease individuals and 95 control individuals did not show an association of these polymorphisms with increased susceptibility to infectious or inflammatory lu
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	p67 phox	1.0	nadph oxidase components p47 phox p67 phox and nox4 but not nox2 were expressed in lung fibroblasts and p67 phox was induced by rhinovirus accompanied by increased ros and elaboration of il 8 [ 27 ].
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	nadph oxidase	1.0	nadph oxidase components p47 phox p67 phox and nox4 but not nox2 were expressed in lung fibroblasts and p67 phox was induced by rhinovirus accompanied by increased ros and elaboration of il 8 [ 27 ].
6025	IL8	interleukin 8	il 8	1.0	nadph oxidase components p47 phox p67 phox and nox4 but not nox2 were expressed in lung fibroblasts and p67 phox was induced by rhinovirus accompanied by increased ros and elaboration of il 8 [ 27 ].
4910	HIF1A	hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)	hypoxia inducible factor 1	1.0	hypoxia hypoxia sensing and related signaling events including activation of hypoxia inducible factor 1 hif 1 represent important features of lung cell physiology and lung function.
4910	HIF1A	hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)	hif 1	1.0	hypoxia hypoxia sensing and related signaling events including activation of hypoxia inducible factor 1 hif 1 represent important features of lung cell physiology and lung function.
4910	HIF1A	hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)	hif 1	1.0	up regulation of nox1 mrna and protein occurred during hypoxia accompanied by enhanced reactive oxygen species ros generation; the latter was accompanied by activation of hif 1 dependent gene expression which was blocked by catalase.
4910	HIF1A	hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)	hif 1	1.0	thus hypoxic upregulation of nox1 and subsequently augmented ros generation may activate hif 1 dependent pathways and participate in adaptation to high altitude [ 40 ].
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	nadph oxidase	1.0	in addition pollen itself contains an endogenous nadph oxidase activity which functions to generate local signals in airway epithelium.
6886	MAPK9	mitogen-activated protein kinase 9	jun kinase	1.0	ary hypertension human urotensin ii which is implicated in pulmonary hypertension potently induced p22 phox and nox4 in lung smooth muscle markedly increasing ros levels that activate erk1 2 p38 mapk jun kinase and akt.
2577	CYBA	cytochrome b-245, alpha polypeptide	p22 phox	1.0	nox and pulmonary hypertension human urotensin ii which is implicated in pulmonary hypertension potently induced p22 phox and nox4 in lung smooth muscle markedly increasing ros levels that activate erk1 2 p38 mapk jun kinase and akt.
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	nox2 and associated regulatory proteins are also expressed in adventitia where they contribute to constitutive ros generation [ 49 ] and to angiotensin ii induced vascular tone in part through inactivation of no by superoxide [ 50 ].
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	increased ros is also associated with left ventricular hypertrophy lvh and this correlated with overexpression of nox2 in angiotensin ii induced lvh and in pressure overload lvh with both nox4 [ 55 ] and nox2 [ 56 ].
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	aldosterone/angiotensin ii mediated interstitial cardiac fibrosis is mediated by nox2 dependent ros generation [ 57 ].
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	enzymes participate in vascular smooth muscle signaling: nox derived ros in vascular smooth muscle cells regulate the activity of the signaling proteins p38 mapk and akt [ 42 ] and are essential for angiotensin ii induced calcium fluxes petumnetcha and lambeth unpublished .
9052	PLAU	plasminogen activator, urokinase	urokinase plasminogen activator	1.0	nox enzymes particularly nox1 and ros are induced in vascular cells by growth stimuli [angiotensin ii pdgf lyso phosphatidylcholine thrombin [ 42 44 64 ] urokinase plasminogen activator [ 65 ] by pgf2_amp_#x003b1; and atf 1 [ 66 ]] and by inflammatory stimuli [e.g. tnf_amp_#x003b1; and il1_amp_#x003b2; [ 67 ]].
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	nox enzymes particularly nox1 and ros are induced in vascular cells by growth stimuli [angiotensin ii pdgf lyso phosphatidylcholine thrombin [ 42 44 64 ] urokinase plasminogen activator [ 65 ] by pgf2_amp_#x003b1; and atf 1 [ 66 ]] and by inflammatory stimuli [e.g. tnf_amp_#x003b1; and il1_amp_#x003b
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	in the latter animals overexpression of nox1 and to a lesser extent nox4 was dependent upon angiotensin ii type 1 receptors.
2577	CYBA	cytochrome b-245, alpha polypeptide	p22 phox	1.0	in mice overexpression in vascular smooth muscle of nox1 [ 70 ] or of p22 phox [ 71 ] which indirectly increases nox1 expression [ 72 ] resulted in a marked increase in systolic blood pressure and hypertrophy in response to angiotensin ii.
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	n vascular smooth muscle of nox1 [ 70 ] or of p22 phox [ 71 ] which indirectly increases nox1 expression [ 72 ] resulted in a marked increase in systolic blood pressure and hypertrophy in response to angiotensin ii.
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	in nox1 knockout mice there was a lowering of basal blood pressure [ 73 ] and a complete protection against angiotensin ii induced increase in blood pressure and medial hypertrophy [ 73 74 ] which resulted in part from sparing of no when superoxide production was eliminated.
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	angiotensin ii induced vasoconstriction and reduced blood flow in kidney also occurred by mechanisms that are independent of no and involved superoxide rather than hydrogen peroxide as a mediator [ 75 ].
9958	REN	renin	renin	1.0	in low renin salt sensitive hypertension a tat peptide inhibitor of nox2 normalized ros generation and endothelium dependent vascular relaxation [ 77 ].
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	nitric oxide synthase	1.0	the mechanisms by which nox derived oxidative stress induces atherogenesis and arterial disease may include direct molecular damage by ros [including _amp_#x0201c;uncoupling_amp_#x0201d; of nitric oxide synthase that results in a further increase in ros [ 85 ]] increased expression of pro atherosclerotic genes [ 42 ] induced differentiation of adventitial fibroblasts into myofibroblasts a feature of the vasc
9393	PRKCA	protein kinase C, alpha	protein kinase c	1.0	this link involves biochemical abnormalities including increased polyol pathway flux increased formation of advanced glycation end products ages activation of protein kinase c and increased flux through the hexosamine pathway.
9393	PRKCA	protein kinase C, alpha	protein kinase c	1.0	for example glycated bsa stimulated nox2 dependent ros production via a protein kinase c dependent mechanism resulting in nf kappab activation and induction of inflammatory genes [ 98 ].
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	in kidney nox dependent ros is produced in response to agonists that bind to d1 like receptors [ 103 ] to angiotensin ii [ 104 105 ] and to h + fluxes [ 106 ].
3415	EPO	erythropoietin	erythropoietin	1.0	although physiological roles are not well understood nox enzymes have been suggested to function in normal renal physiology in secretion of erythropoietin [ 100 ] in renal regulation of blood pressure [ 103 ] regulation of mesangial cell protein synthesis [ 107 ] and in innate immunity [ 23 ].
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensinogen	1.0	in proximal tubules high glucose stimulates ros production resulting in increased expression of angiotensinogen [ 108 ] with consequent systemic effects e.g. on blood pressure.
9395	PRKCB1	protein kinase C, beta 1	pkc beta	1.0	pkc beta _amp_#x02212;/_amp_#x02212; diabetic mice were protected against induction of nox2 nox4 and glucose induced renal dysfunction and fibrosis indicating a role for pkc in nox expression and renal pathol
2577	CYBA	cytochrome b-245, alpha polypeptide	p22 phox	1.0	likewise glomerular mesangial injury in rats treated chronically with aldosterone and salt is associated with induction of nox2 nox4 and p22 phox [ 114 ] increased p47 phox and p67 phox in the membrane fraction indicating activation of the nox2 system and increased renal ros and [ 102 ].
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	p67 phox	1.0	likewise glomerular mesangial injury in rats treated chronically with aldosterone and salt is associated with induction of nox2 nox4 and p22 phox [ 114 ] increased p47 phox and p67 phox in the membrane fraction indicating activation of the nox2 system and increased renal ros and [ 102 ].
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	in an angiotensin ii induced mesangioproliferative model of glomerulonephritis nox2 and nox4 induction were associated with disease progression and treatment with the antioxidant probucol in combination with angiotensin
336	AGTR1	angiotensin II receptor, type 1	angiotensin ii receptor	1.0	giotensin ii induced mesangioproliferative model of glomerulonephritis nox2 and nox4 induction were associated with disease progression and treatment with the antioxidant probucol in combination with angiotensin ii receptor blockade fully arrested disease progression and proteinuria [ 115 ].
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	angiotensin ii infused rodents show increased renal and systemic expression of nox1 [ 117 ] which contributes to the development and maintenance of hypertension.
9393	PRKCA	protein kinase C, alpha	protein kinase c	1.0	regulation of tubular transport by ros is important to overall salt and water balance and therefore to blood pressure: superoxide stimulates nacl absorption by the thick ascending limb by activating protein kinase c and by blunting the effects of no [ 119 ].
5173	HRAS	v-Ha-ras Harvey rat sarcoma viral oncogene homolog	k ras	1.0	over expression showed a strong correlation with oncogenic mutations in k ras and markedly elevated nox1 levels in the intestinal tract were also seen in mice that expressed v12 k ras in intestinal epithelium.
5173	HRAS	v-Ha-ras Harvey rat sarcoma viral oncogene homolog	k ras	1.0	these studies are consistent with earlier studies in a v12 k ras expressing model epithelial cell line that showed a marked induction of nox1 mrna and ros [ 137 ].
5173	HRAS	v-Ha-ras Harvey rat sarcoma viral oncogene homolog	k ras	1.0	decreasing the expression of nox1 originally called mox1 decreased cell division in vascular smooth muscle [ 46 ] and in v12 k ras transformed nrk cells [ 137 ].
1516	CAT	catalase	catalase	1.0	in fibroblasts that over expressed heterologous nox1 and also harbored an oncogenic mutation in ras overexpression of catalase markedly decreased mitogenic growth the transformed phenotype and tumorigenicity in athymic mice [ 140 ] implicating nox derived h 2 o 2 in the tumor phenotype.
1582	CCND1	cyclin D1	cyclin d1	1.0	in actively cycling cells nox1 stimulated proliferation by reducing the requirement for growth factors to maintain expression of cyclin d1 whereas during cell cycle re entry nox1 activity was required for transcriptional activation of fos family genes [ 138 ].
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	nf kappa b	1.0	cell survival involved activation of nf kappa b [ 136 ] and akt [ 142 ] dependent pro survival pathways.
11132	SNAP25	synaptosomal-associated protein, 25kDa	snap25	1.0	a possible target is the fusion protein snap25 which may function as a presynaptic ros sensor [ 155 ].
11517	TAC1	tachykinin, precursor 1	substance p	1.0	in a more natural setting substance p produced in substantia nigra can also activate glial nox2 and could play a role in pd [ 177 ].
11764	TG	thyroglobulin	thyroglobulin	1.0	duox and the thyroid gland the thyroid gland carries out the thyroid peroxidase dependent iodination of thyroglobulin a key step in the biosynthesis of thyroid hormone.
12015	TPO	thyroid peroxidase	thyroid peroxidase	1.0	duox and the thyroid gland the thyroid gland carries out the thyroid peroxidase dependent iodination of thyroglobulin a key step in the biosynthesis of thyroid hormone.
14874	NOX5	NADPH oxidase, EF-hand calcium binding domain 5	nadph oxidase	1.0	this reaction requires h 2 o 2 which derives from a previously unidentified thyroid nadph oxidase.
6081	INS	insulin	insulin	1.0	pancreatic islets diabetes and nox enzymes nox1 nox2 and nox4 were found in pancreatic islet cells and glucose stimulated insulin secretion was suppressed by a general nox inhibitor supporting a role for one or more nox enzymes in normal pancreatic islet function [ 194 ].
6081	INS	insulin	insulin	1.0	in early type 1 diabetes systemic markers of oxidative stress correlate with insulin requirements suggesting that oxidative stress in the pancreatic islets damages insulin secreting beta cells [ 195 ].
6081	INS	insulin	insulin	1.0	in type ii diabetes increased expression of nox1 occurs in islets and may exacerbate disease over time by damaging insulin producing cells [ 196 ].
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	signaling role of nox enzymes in hormonal responses nox1 induction and activation is implicated in the hormonal response to angiotensin ii and growth factors such as pdgf and egf vide infra .
6081	INS	insulin	insulin	1.0	in addition recent studies implicate nox4 in the tissue response to insulin [ 198 199 ].
6081	INS	insulin	insulin	1.0	in fat cells insulin triggered h 2 o 2 production; h 2 o 2 was essential for transduction of the insulin signal in part by ros inhibition of the protein tyrosine phosphatase ptp1b.
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	additional studies m petumnetcha and d lambeth unpublished show that the angiotensin ii stimulated calcium flux human vascular smooth muscle is likewise dependent upon the generation of a nox probably nox1 generated h 2 o 2 signal.
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	chronic granulomatous disease	1.0	in many cases the role of a nox enzyme has been established either by human or mouse mutations chronic granulomatous disease gravity perception hypothyroidism or by convincing cellular studies while in other cases the evidence is still circumstantial.