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PMID	17167116 ( )
Title	Oxidants in chronic kidney disease.
Abstract	Chronic kidney disease is a worldwide public health problem that affects approximately 10% of the US adult population and is associated with a high prevalence of cardiovascular disease and high economic cost. Chronic renal insufficiency, once established, tends to progress to end-stage kidney disease, suggesting some common mechanisms for ultimately causing scarring and further nephron loss. This review defines the term reactive oxygen metabolites (ROM), or oxidants, and presents the available experimental evidence in support of the role of oxidants in diabetic and nondiabetic glomerular disease and their role in tubulointerstitial damage that accompanies progression. It concludes by reviewing the limited human data that provide some proof of concept that the observations in experimental models may be relevant to human disease. Slot 501, Little Rock, AR 72205, USA. shahsudhirv@uams.edu

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
10618	CCL2	chemokine (C-C motif) ligand 2	11	monocyte chemoattractant protein 1 \| mcp 1 \| MCP-1 \|
6871	MAPK1	mitogen-activated protein kinase 1	9	ERK \| ERK-directed \| extracellular signal regulated kinase \| p38 \| MAPK \|
11766	TGFB1	transforming growth factor, beta 1	5	TGF-beta1 \|
399	ALB	albumin	4	albumin \|
6025	IL8	interleukin 8	4	IL-8 \| il 8 \|
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	4	NF-kappaB-dependent \|
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	4	angiotensin ii \| ang i \| ang ii \|
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	4	superoxide dismutase \|
11740	TF	transferrin	3	transferrin \|
7218	MPO	myeloperoxidase	3	myeloperoxidase \| MPO \|
7891	NOX4	NADPH oxidase 4	3	Nox4 \|
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	2	Nox2 \|
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	2	Akt \| protein kinase b \|
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	2	ap 1 \| AP-1 \|
9393	PRKCA	protein kinase C, alpha	2	protein kinase c \|
6081	INS	insulin	2	insulin \|
990	BCL2	B-cell CLL/lymphoma 2	2	Bcl-2 \| bcl 2 \|
1516	CAT	catalase	2	catalase \|
2707	ACE	angiotensin I converting enzyme (peptidyl-dipeptidase A) 1	2	ACE \| angiotensin converting enzyme \|
9954	REL	v-rel reticuloendotheliosis viral oncogene homolog (avian)	1	c rel \|
24692	FCAMR	Fc receptor, IgA, IgM, high affinity	1	fc receptor \|
9600	PTGFR	prostaglandin F receptor (FP)	1	PGF \|
11609	TBXAS1	thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A)	1	cytochrome p450 \|
6768	SMAD2	SMAD family member 2	1	smad 2 \|
3176	EDN1	endothelin 1	1	ET-1 \|
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	1	caspase 3 \|
11919	CD40	CD40 molecule, TNF receptor superfamily member 5	1	p50 \|
12805	XDH	xanthine dehydrogenase	1	xanthine oxidase \|
19986	CYCS	cytochrome c, somatic	1	cytochrome c \|
2615	CYP2B6	cytochrome P450, family 2, subfamily B, polypeptide 6	1	P450 \|
6877	MAPK3	mitogen-activated protein kinase 3	1	ERK1 \|
166	ACTN4	actinin, alpha 4	1	FSGS \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
2707	ACE	angiotensin I converting enzyme (peptidyl-dipeptidase A) 1	ACE	0.6	of kidney disease has been reasonably well established only with ACE inhibitors and ARB
7218	MPO	myeloperoxidase	MPO	1.3	metabolism of H 2 O 2 by neutrophil-derived myeloperoxidase (MPO; MPO the enzyme that is responsible for the green color of
7218	MPO	myeloperoxidase	MPO	1.3	Infusion of MPO followed by H 2 O 2 results in significant proteinuria
6871	MAPK1	mitogen-activated protein kinase 1	ERK	1.9	reduced generation of oxidants reduced phosphorylated extracellular signal-regulated kinase (ERK), ERK significant improvement in glomerular injury as measured histologically and reduced
11766	TGFB1	transforming growth factor, beta 1	TGF-beta1	0.3	in glomerular injury as measured histologically and reduced expression of TGF-beta1 ( 25
2615	CYP2B6	cytochrome P450, family 2, subfamily B, polypeptide 6	P450	1.9	( 34 recently demonstrated that cytochrome P450_amp_#151 more specific cytochrome P450 2B1 an isozyme that is present in the glomerulus_amp_#151 is
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	1.3	termed Nox proteins correspond to homologues of gp91 (or or Nox2 the catalytic moiety found in phagocytes
7891	NOX4	NADPH oxidase 4	Nox4	0.8	Nox4 which seems to share the same overall structure with gp91
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	Nox2	1.3	seems to share the same overall structure with gp91 /Nox2, Nox2 is abundant in the vascular system kidney cortex and mesangial
7891	NOX4	NADPH oxidase 4	Nox4	0.8	( 56 showed that Nox4 protein expression is increased in the diabetic kidney cortex and
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	1.9	( 49 including PKC ( 49 mitogen-activated protein kinases (MAPK), MAPK TGF-beta1 ( 60 and fibronectin ( 60 61
11766	TGFB1	transforming growth factor, beta 1	TGF-beta1	0.3	49 including PKC ( 49 mitogen-activated protein kinases (MAPK), MAPK TGF-beta1 ( 60 and fibronectin ( 60 61
11766	TGFB1	transforming growth factor, beta 1	TGF-beta1	0.3	Antioxidants also prevent upregulation of TGF-beta1 ( 62 66 and fibronectin ( 62 and activation of
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	AP-1	1.3	fibronectin ( 62 and activation of transcription factors NF-kappaB and AP-1 in mesangial cells ( 61
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	66 and fibronectin ( 62 and activation of transcription factors NF-kappaB and AP-1 in mesangial cells ( 61
10618	CCL2	chemokine (C-C motif) ligand 2	MCP-1	2.3	and oxidants resulting in upregulation of monocyte chemoattractant protein-1 (MCP-1) MCP-1 mRNA and protein expression
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	( 61 showed that high glucose rapidly activates NF-kappaB in mesangial cells through PKC and oxidants resulting in upregulation
3176	EDN1	endothelin 1	ET-1	0.3	The higher endothelin (ET-1) ET-1 in glomeruli that are isolated from diabetic rats is attenuated
7891	NOX4	NADPH oxidase 4	Nox4	0.8	( 56 showed that in vivo inhibition of Nox4 by antisense reduced whole-kidney and glomerular hypertrophy accompanied by reduced
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	Akt	0.6	hypertrophy accompanied by reduced expression of fibronectin protein and Akt/protein Akt protein kinase B and ERK1/2, ERK1 2 two protein kinases
6877	MAPK3	mitogen-activated protein kinase 3	ERK1	2.4	fibronectin protein and Akt/protein Akt protein kinase B and ERK1/2, ERK1 2 two protein kinases that are critical for cell growth
11766	TGFB1	transforming growth factor, beta 1	TGF-beta1	0.3	antioxidants prevent glomerular and renal hypertrophy albuminuria glomerular expression of TGF-beta1 and extracellular matrix and PKC activation in experimental diabetes (
11766	TGFB1	transforming growth factor, beta 1	TGF-beta1	0.3	plasma glucose levels in both normal and diabetic rats that TGF-beta1 is a pro-oxidant and that selenium deficiency increases oxidative stress
6871	MAPK1	mitogen-activated protein kinase 1	p38	1.9	There was activation of p38 MAPK and caspase 3
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	1.9	There was activation of p38 MAPK and caspase 3
11919	CD40	CD40 molecule, TNF receptor superfamily member 5	p50	0.3	p65 c-Rel binding activity and suppressed binding activity of the p50 dimer
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.0	by glucose-induced oxidant stress included the heterodimeric redox-sensitive transcription factor NF-kappaB which exhibited an upregulation in p65/c-Rel p65 c-Rel binding activity
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.0	Perturbations in the expression and phosphorylation of the Bcl-2 family were coupled with the release of cytochrome c from
10618	CCL2	chemokine (C-C motif) ligand 2	MCP-1	2.3	MCP-1 has been identified as a product of a gene that
6025	IL8	interleukin 8	IL-8	1.3	IL-8 is a key proinflammatory chemokine responsible for recruiting and activating
10618	CCL2	chemokine (C-C motif) ligand 2	MCP-1	2.3	to activation of NF-kappaB-dependent pathways resulting in increased expression of MCP-1 and IL-8 which are important in the inflammatory response (
6025	IL8	interleukin 8	IL-8	1.3	of NF-kappaB-dependent pathways resulting in increased expression of MCP-1 and IL-8 which are important in the inflammatory response ( 76 77
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB-dependent	0.0	H 2 O 2 production which leads to activation of NF-kappaB-dependent pathways resulting in increased expression of MCP-1 and IL-8 which
10618	CCL2	chemokine (C-C motif) ligand 2	MCP-1	2.3	of oxidants through xanthine oxidase resulting in increased expression of MCP-1 and vascular cellular adhesion molecule-1 and macrophage infiltration in the
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	1.9	EMT in renal tubular epithelial cells directly through activation of MAPK and indirectly through ERK-directed Smad 2 phosphorylation and suggested that
6871	MAPK1	mitogen-activated protein kinase 1	ERK-directed	1.9	epithelial cells directly through activation of MAPK and indirectly through ERK-directed Smad 2 phosphorylation and suggested that antioxidants and MAPK inhibitors
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	1.9	through ERK-directed Smad 2 phosphorylation and suggested that antioxidants and MAPK inhibitors may prevent EMT through both MAPK and Smad pathways
6871	MAPK1	mitogen-activated protein kinase 1	MAPK	1.9	that antioxidants and MAPK inhibitors may prevent EMT through both MAPK and Smad pathways and subsequent tubulointerstitial fibrosis
9600	PTGFR	prostaglandin F receptor (FP)	PGF	0.3	of F2 isoprostane 8-iso prostaglandin F 2 alpha (8-iso 8-iso PGF 2 alpha which is a widely recognized marker of oxidative
10618	CCL2	chemokine (C-C motif) ligand 2	MCP-1	2.3	signification reduction in 8-iso-PGF2 alpha accompanied by a reduction in MCP-1 and urinary albumin
166	ACTN4	actinin, alpha 4	FSGS	1.0	products of lipid peroxidation were increased significantly in patients with FSGS and concluded that oxidative stress occurs early and may play
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	tion that oxidants may be important in inflammation and tissue injury first was suggested by joe mccord a graduate student with dr. irwin fridovich at duke university who in 1969 described the enzyme superoxide dismutase.
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	they labeled this protein orgotein and quickly recognized its identity with superoxide dismutase on the basis of the physical and spectral characteristics.
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	he reasoned that because phagocytosing neutrophils the effector cells of the acute inflammatory response release large amounts of superoxide extracellularly and superoxide dismutase an enzyme that scavenges superoxide possesses anti inflammatory activity superoxide anion and other oxygen metabolites could be important mediators of the inflammatory process 6 7 .
399	ALB	albumin	albumin	1.0	this is in keeping with the data that albumin itself seems to have significant effects on tubular cells including enhanced generation of oxidants and activation of the inflammatory response.
7218	MPO	myeloperoxidase	myeloperoxidase	1.0	the metabolism of h 2 o 2 by neutrophil derived myeloperoxidase mpo; the enzyme that is responsible for the green color of pus generates highly reactive toxic products including hypochlorous acid hocl the active ingredient in clorox bleach .
11740	TF	transferrin	transferrin	1.0	because iron can participate in the formation of rom organisms take great care in the handling of iron using transport proteins such as transferrin and storage proteins such as ferritin and minimizing the size of the intracellular iron pool.
24692	FCAMR	Fc receptor, IgA, IgM, high affinity	fc receptor	1.0	several immune reactants such as serum treated zymosan a c 3 b receptor stimulus heat aggregated igg an fc receptor stimulus immune complexes complement components and antinuclear antibody 15 all have been shown to trigger the oxidative burst.
1516	CAT	catalase	catalase	1.0	n to this in vitro observation infusion of phorbol myristate acetate a potent activator of leukocytes or of cobra venom factor in the renal artery caused significant proteinuria that was prevented by catalase which destroys h 2 o 2 and neutrophil depletion 17 19 .
1516	CAT	catalase	catalase	1.0	in an anti gbm antibody model treatment with catalase markedly reduced proteinuria 23 and a hydroxyl radical scavenger or iron chelator significantly attenuated proteinuria 24 .
6871	MAPK1	mitogen-activated protein kinase 1	extracellular signal regulated kinase	1.0	in an anti thy 1.1 model treatment with antioxidant alpha lipolic acid resulted in reduced generation of oxidants reduced phosphorylated extracellular signal regulated kinase erk significant improvement in glomerular injury as measured histologically and reduced expression of tgf beta1 25 .
11609	TBXAS1	thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A)	cytochrome p450	1.0	34 recently demonstrated that cytochrome p450_amp_#151;more specific cytochrome p450 2b1 an isozyme that is present in the glomerulus_amp_#151;is a source of catalytic iron that participates in glomerular injury in this model 35 36 table 2 .
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	superoxide dismutase	1.0	similarly inhibition of superoxide dismutase augments pan induced proteinuria 38 .
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	angiotensin ii	1.0	in this section we emphasize some of the recent developments including the pathways that are responsible for enhanced generation of oxidants the relation between angiotensin ii angii and oxidants and some of the newer mechanisms for diabetic nephropathy in which oxidants play an important role.
9393	PRKCA	protein kinase C, alpha	protein kinase c	1.0	recent studies suggest the important role of nad p h oxidase 55 and protein kinase c pkc 49 50 in enhanced oxidant production in diabetes.
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	ang ii	1.0	there is evidence that the renoprotective effects of ang ii type 1 receptor blockers arb and angiotensin converting enzyme inhibitors acei independent of lowering bp may be related to the effects on oxidant stress 57 .
2707	ACE	angiotensin I converting enzyme (peptidyl-dipeptidase A) 1	angiotensin converting enzyme	1.0	there is evidence that the renoprotective effects of ang ii type 1 receptor blockers arb and angiotensin converting enzyme inhibitors acei independent of lowering bp may be related to the effects on oxidant stress 57 .
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	ang i	1.0	it has been shown that incubation of mesangial cells in high glucose results in an increase in ang i and ang ii levels and an increase in superoxide which is mediated through the nad p h oxidase system 58 .
333	AGT	angiotensinogen (serpin peptidase inhibitor, clade A, member 8)	ang ii	1.0	it has been shown that incubation of mesangial cells in high glucose results in an increase in ang i and ang ii levels and an increase in superoxide which is mediated through the nad p h oxidase system 58 .
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	ap 1	1.0	antioxidants also prevent upregulation of tgf beta1 62 66 and fibronectin 62 and activation of transcription factors nf kappab and ap 1 in mesangial cells 61 .
10618	CCL2	chemokine (C-C motif) ligand 2	mcp 1	1.0	61 showed that high glucose rapidly activates nf kappab in mesangial cells through pkc and oxidants resulting in upregulation of monocyte chemoattractant protein 1 mcp 1 mrna and protein expression.
10618	CCL2	chemokine (C-C motif) ligand 2	monocyte chemoattractant protein 1	1.0	61 showed that high glucose rapidly activates nf kappab in mesangial cells through pkc and oxidants resulting in upregulation of monocyte chemoattractant protein 1 mcp 1 mrna and protein expression.
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	protein kinase b	1.0	56 showed that in vivo inhibition of nox4 by antisense reduced whole kidney and glomerular hypertrophy accompanied by reduced expression of fibronectin protein and akt/protein kinase b and erk1/2 two protein kinases that are critical for cell growth and hypertrophy.
1504	CASP3	caspase 3, apoptosis-related cysteine peptidase	caspase 3	1.0	there was activation of p38 mapk and caspase 3.
399	ALB	albumin	albumin	1.0	inhibition of nad p h oxidase prevented apoptosis and reduced podocyte depletion urinary albumin excretion and mesangial matrix expansion.
9954	REL	v-rel reticuloendotheliosis viral oncogene homolog (avian)	c rel	1.0	the signaling cascade that is activated by glucose induced oxidant stress included the heterodimeric redox sensitive transcription factor nf kappab which exhibited an upregulation in p65/c rel binding activity and suppressed binding activity of the p50 dimer.
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	perturbations in the expression and phosphorylation of the bcl 2 family were coupled with the release of cytochrome c from mitochondria and caspase activation.
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	perturbations in the expression and phosphorylation of the bcl 2 family were coupled with the release of cytochrome c from mitochondria and caspase activation.
399	ALB	albumin	albumin	1.0	morigi et al. have shown that human proximal tubular cells incubated with human albumin 1 to 30 mg/ml and igg lead to a significant and rapid increase in h 2 o 2 and activation of nf kappa beta.
9393	PRKCA	protein kinase C, alpha	protein kinase c	1.0	inhibitors of protein kinase c significantly prevented h 2 o 2 production and consequent nf kappa beta activation 76 figure 2 ; table 4 .
10618	CCL2	chemokine (C-C motif) ligand 2	mcp 1	1.0	mcp 1 has been identified as a product of a gene that belongs to the small inducible cytokine family that is known in the murine system as the je gene.
6025	IL8	interleukin 8	il 8	1.0	il 8 is a key proinflammatory chemokine responsible for recruiting and activating neutrophils t cells and monocytes.
399	ALB	albumin	albumin	1.0	it has been shown that albumin is a strong stimulus for h 2 o 2 production which leads to activation of nf kappab dependent pathways resulting in increased expression of mcp 1 and il 8 which are important in the inflammatory respo
10618	CCL2	chemokine (C-C motif) ligand 2	mcp 1	1.0	it has been shown that albumin is a strong stimulus for h 2 o 2 production which leads to activation of nf kappab dependent pathways resulting in increased expression of mcp 1 and il 8 which are important in the inflammatory response 76 77 .
6025	IL8	interleukin 8	il 8	1.0	it has been shown that albumin is a strong stimulus for h 2 o 2 production which leads to activation of nf kappab dependent pathways resulting in increased expression of mcp 1 and il 8 which are important in the inflammatory response 76 77 .
10618	CCL2	chemokine (C-C motif) ligand 2	mcp 1	1.0	78 showed in an in vivo model that hyperlipidemia leads to increased generation of oxidants through xanthine oxidase resulting in increased expression of mcp 1 and vascular cellular adhesion molecule 1 and macrophage infiltration in the tubulointerstitial region.
12805	XDH	xanthine dehydrogenase	xanthine oxidase	1.0	78 showed in an in vivo model that hyperlipidemia leads to increased generation of oxidants through xanthine oxidase resulting in increased expression of mcp 1 and vascular cellular adhesion molecule 1 and macrophage infiltration in the tubulointerstitial region.
6768	SMAD2	SMAD family member 2	smad 2	1.0	80 showed that ros mediate tgf beta1 induced emt in renal tubular epithelial cells directly through activation of mapk and indirectly through erk directed smad 2 phosphorylation and suggested that antioxidants and mapk inhibitors may prevent emt through both mapk and smad pathways and subsequent tubulointerstitial fibrosis.
11740	TF	transferrin	transferrin	1.0	the sources of increased iron in the kidney have not been well delineated but alfrey and colleagues 83 84 suggested that urinary transferrin provides a potential source of iron.
6081	INS	insulin	insulin	1.0	several reports described an increase in the 8 oxodg content in the urine of patients with type 1 insulin dependent and type 2 non insulin dependent diabetes 92 94 with the levels being significantly higher in patients with albuminuria figure 3b or with other diabetic complications 95 .
6081	INS	insulin	insulin	1.0	in this context it is relevant that insulin decreases nad p h oxidase activity 92 .
11740	TF	transferrin	transferrin	1.0	it is interesting that recent studies have demonstrated that non transferrin bound iron levels frequently are increased in diabetes and have been implicated in a few studies with the vascular complications of diabetes 100 .
10618	CCL2	chemokine (C-C motif) ligand 2	mcp 1	1.0	104 showed that spironolactone treatment in patients with diabetic nephropathy caused a signification reduction in 8 iso pgf2 alpha accompanied by a reduction in mcp 1 and urinary albumin.