Document Information

PMID 11786100  (  )
Title Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: effects of ACEI and ARB.
Abstract BACKGROUND: Angiotensin II (Ang II) can up-regulate nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase, whose product superoxide anion (O2-) can interact with nitric oxide (NO) to form peroxynitrite (ONOO-). We tested the hypothesis that Ang II subtype 1 (AT1) receptor activation enhances oxidative stress and nitrotyrosine deposition in the kidneys of rats with diabetes mellitus (DM). METHODS: After two weeks of streptozotocin-induced DM, rats received either no treatment, an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) for two weeks. At four weeks, renal expression of the p47phox component of NAD(P)H oxidase, endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and nitrotyrosine were evaluated by Western blot and immunohistochemistry and related to plasma lipid peroxidation products (LPO), hydrogen peroxide production in the kidney and 24-hour protein excretion. RESULTS: Immunoreactive expression of p47phox and eNOS were increased in DM with an increase in plasma LPO, renal hydrogen peroxide production and nitrotyrosine deposition. Expression of nNOS was unaltered. Treatment with either ACEI or ARB prevented all these findings and also prevented significant microalbuminuria. The treatments did not affect the elevated blood sugar, nor did DM or its treatment affect the blood pressure or the creatinine clearance. CONCLUSION: Early proteinuric diabetic nephropathy increases renal expression of the p47phox component of NAD(P)H oxidase and eNOS with increased indices of systemic and renal oxidative/nitrosative stress. An ACEI or an ARB prevents these changes and prevents the development of proteinuria, independent of blood pressure or blood sugar. This finding indicates a pathogenic role for AT1 receptors in the development of oxidative damage in the kidneys during early DM. Japan.

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Targets by SciMiner Summary

HUGO ID Symbol Target Name #Occur ActualStr
7876NOS3nitric oxide synthase 3 (endothelial cell)30endothelial nitric oxide synthase | eNOS-induced |
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)26p47phox-induced |
7872NOS1nitric oxide synthase 1 (neuronal)21NOS | nNOS | neuronal nitric oxide synthase |
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)9angiotensin ii | ang ii | Ang |
399ALBalbumin8albumin |
2707ACEangiotensin I converting enzyme (peptidyl-dipeptidase A) 15angiotensin converting enzyme |
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)4nitric oxide synthase |
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)4gp91phox |
7661NCF2neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)3p67phox |
2577CYBAcytochrome b-245, alpha polypeptide3p22phox |
11766TGFB1transforming growth factor, beta 12TGF-beta1 | transforming growth factor beta1 |
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))2SOD | superoxide dismutase |
12805XDHxanthine dehydrogenase1xanthine oxidase |
6081INSinsulin1insulin |
11362STAT1signal transducer and activator of transcription 1, 91kDa1STAT |
7662NCF4neutrophil cytosolic factor 4, 40kDa1p40phox |
14874NOX5NADPH oxidase, EF-hand calcium binding domain 51nadph oxidase |
7889NOX1NADPH oxidase 11MOX-1 |
11765TGFAtransforming growth factor, alpha1transforming growth factor |
7891NOX4NADPH oxidase 41Renox |

 

Targets by SciMiner Full list

HUGO ID Symbol Name ActualStr Score FlankingText
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0At four weeks renal expression of the p47phox component of NAD(P)H NAD P H oxidase endothelial nitric oxide
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0NAD(P)H NAD P H oxidase endothelial nitric oxide synthase (eNOS), eNOS neuronal nitric oxide synthase (nNOS), nNOS and nitrotyrosine were evaluated
7872NOS1nitric oxide synthase 1 (neuronal)nNOS3.2nitric oxide synthase (eNOS), eNOS neuronal nitric oxide synthase (nNOS), nNOS and nitrotyrosine were evaluated by Western blot and immunohistochemistry and
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0Results Immunoreactive expression of p47phox and eNOS were increased in DM with an increase in
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0Results Immunoreactive expression of p47phox and eNOS were increased in DM with an increase in plasma LPO
7872NOS1nitric oxide synthase 1 (neuronal)nNOS3.2Expression of nNOS was unaltered
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0Conclusion Early proteinuric diabetic nephropathy increases renal expression of the p47phox component of NAD(P)H NAD P H oxidase and eNOS with
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0the p47phox component of NAD(P)H NAD P H oxidase and eNOS with increased indices of systemic and renal oxidative/nitrosative oxidative nitrosative
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.3There are two membrane-associated proteins p22phox and gp91phox and three major cytosolic components p47phox p40phox and
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox1.3There are two membrane-associated proteins p22phox and gp91phox and three major cytosolic components p47phox p40phox and p67phox 10
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0membrane-associated proteins p22phox and gp91phox and three major cytosolic components p47phox p40phox and p67phox 10
7662NCF4neutrophil cytosolic factor 4, 40kDap40phox2.2proteins p22phox and gp91phox and three major cytosolic components p47phox p40phox and p67phox 10
7661NCF2neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)p67phox2.2and gp91phox and three major cytosolic components p47phox p40phox and p67phox 10
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox1.3While endothelial cells express gp91phox rodent vascular smooth muscle cells express a different isoform termed
7889NOX1NADPH oxidase 1MOX-10.9rodent vascular smooth muscle cells express a different isoform termed MOX-1 11 and in the kidney the gp91phox is replaced in
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox1.3different isoform termed MOX-1 11 and in the kidney the gp91phox is replaced in certain tubule cells with another isoform termed
7891NOX4NADPH oxidase 4Renox1.9is replaced in certain tubule cells with another isoform termed Renox 12
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0The p47phox is extensively regulated
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0Up-regulation of p47phox is seen in the kidneys of spontaneously hypertensive rat (SHR),
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0In vascular smooth muscle cells p47phox is linked to Ang II-dependent JAK/STAT JAK STAT signaling events
11362STAT1signal transducer and activator of transcription 1, 91kDaSTAT0.3muscle cells p47phox is linked to Ang II-dependent JAK/STAT JAK STAT signaling events that underlie proliferation 24
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)Ang0.1In vascular smooth muscle cells p47phox is linked to Ang II-dependent JAK/STAT JAK STAT signaling events that underlie proliferation 24
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0Therefore our initial studies have focused on the p47phox component although in vasculature angiotensin II (Ang Ang II also
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.3although in vasculature angiotensin II (Ang Ang II also up-regulates p22phox 25 and p67phox 26
7661NCF2neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)p67phox2.2angiotensin II (Ang Ang II also up-regulates p22phox 25 and p67phox 26
11766TGFB1transforming growth factor, beta 1TGF-beta11.2increase the expression of the mRNA for transforming growth factor-beta1 TGF-beta1 and fibronectin in the glomerulus 4 5 to decrease the
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD0.9membrane-permeable nitroxide tempol that acts as a superoxide dismutase (SOD) SOD mimetic 9
7872NOS1nitric oxide synthase 1 (neuronal)NOS2.7unclear since other oxidases including constitutive nitric oxide synthase (NOS), NOS lipooxygenase and xanthine oxidase all can contribute to oxidative stress
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0of this study was to evaluate the expression of the p47phox component of NAD(P)H NAD P H oxidase and constitutive NOS
7872NOS1nitric oxide synthase 1 (neuronal)NOS2.7p47phox component of NAD(P)H NAD P H oxidase and constitutive NOS in the kidneys of rats during early streptozotocin-induced experimental diabetes
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0for 30 minutes following overnight incubation with monoclonal antibody for p47phox endothelial nitric oxide synthase (eNOS), eNOS neuronal nitric oxide synthase
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0with monoclonal antibody for p47phox endothelial nitric oxide synthase (eNOS), eNOS neuronal nitric oxide synthase (nNOS; nNOS Transduction Laboratories Lexington KY
7872NOS1nitric oxide synthase 1 (neuronal)nNOS3.2nitric oxide synthase (eNOS), eNOS neuronal nitric oxide synthase (nNOS; nNOS Transduction Laboratories Lexington KY USA and nitrotyrosine (Upstate Upstate Technology
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0peroxidase activity and thereafter with a monoclonal antibody directed against p47phox eNOS and nNOS (Transduction Transduction Laboratories at 1 100 dilution
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0activity and thereafter with a monoclonal antibody directed against p47phox eNOS and nNOS (Transduction Transduction Laboratories at 1 100 dilution for
7872NOS1nitric oxide synthase 1 (neuronal)nNOS3.2thereafter with a monoclonal antibody directed against p47phox eNOS and nNOS (Transduction Transduction Laboratories at 1 100 dilution for four hours
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0Expression of p47phox The p47phox cytosolic component of NAD(P)H NAD P H oxidase
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0Expression of p47phox The p47phox cytosolic component of NAD(P)H NAD P H oxidase was expressed
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0The quantitative analysis of p47phox protein in the kidney by Western blot showed a specific
7872NOS1nitric oxide synthase 1 (neuronal)NOS2.7Expression of NOS isoforms and nitrosylation of proteins Immunohistochemical studies showed expression of
7872NOS1nitric oxide synthase 1 (neuronal)nNOS3.2of proteins Immunohistochemical studies showed expression of type I or nNOS in the macula densa whose expression seemed to be slightly
7872NOS1nitric oxide synthase 1 (neuronal)nNOS3.2kidney homogenates showed a band of 160 kD corresponding to nNOS whose densitometry showed no differences between the four groups (control
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0immunohistochemical study showed a prominent expression of type III or eNOS in the endothelium of glomeruli renal arteries and arterioles that
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0Western blot analysis Figure 5 confirmed a modest increase in eNOS expression in rats with DM (0.29 0.29 0.01 vs 0.24
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0evidence of oxidative stress associated with enhanced renal expression of p47phox and eNOS and nitrotyrosine
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0oxidative stress associated with enhanced renal expression of p47phox and eNOS and nitrotyrosine
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0Hyperglycemia can increase the expression of p47phox in leukocytes 43
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0In this study p47phox expression indeed was enhanced in the kidneys of hyperglycemic diabetic
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0immunohistochemical findings suggest that there may be enhanced expression of p47phox in the cortex and the medulla
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0However our data dissociate the activation of p47phox and eNOS and the development of oxidative stress in DM
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0However our data dissociate the activation of p47phox and eNOS and the development of oxidative stress in DM from hyperglycemia
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0modify the hyperglycemia yet fully prevented the increased expression of p47phox eNOS and their products including nitrotyrosine plasma LPO and renal
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0the hyperglycemia yet fully prevented the increased expression of p47phox eNOS and their products including nitrotyrosine plasma LPO and renal H
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox1.3Recently enhanced gp91phox NADPH oxidase and eNOS expression in aorta have been demonstrated
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0Recently enhanced gp91phox NADPH oxidase and eNOS expression in aorta have been demonstrated in the early stage
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.3stimulated NAD(P)H NAD P H oxidase activity and expression of p22phox and p67phox in VSMCs 25 26 42
7661NCF2neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)p67phox2.2NAD P H oxidase activity and expression of p22phox and p67phox in VSMCs 25 26 42
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0Both the ACEI and the ARB suppressed p47phox expression significantly in the kidney of diabetic rats
7872NOS1nitric oxide synthase 1 (neuronal)NOS2.7NOS and nitrotyrosine expression in the kidney Our findings address the
7872NOS1nitric oxide synthase 1 (neuronal)NOS2.7Our findings address the controversy concerning the contribution of different NOS isoforms to intrarenal production of NO in diabetes
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0We detected an increased expression of eNOS in microvessels and kidneys of rats with DM
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0in rats with early DM detected no changes in renal eNOS protein expression 50
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0relate to the time course of induction of diabetes 21 eNOS is expressed significantly also in tubular epithelial cells which may
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0epithelial cells which may therefore have contributed to the increased eNOS protein expression detected by Western analysis in whole kidneys of
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0However immunohistochemical studies do not detect prominent expression of eNOS protein in tubules 35
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0Therefore tubular expression of eNOS could not be assessed in this study
7872NOS1nitric oxide synthase 1 (neuronal)nNOS3.2We could not confirm an increase in nNOS expression in the kidney of diabetic rats that others reported
7872NOS1nitric oxide synthase 1 (neuronal)nNOS3.2The prior increases in nNOS expression have been related to the accompanying glomerular hyperfiltration
7872NOS1nitric oxide synthase 1 (neuronal)nNOS3.2model of insulinogenic diabetes without insulin replacement no increase in nNOS protein expression in the kidney was detected nor was evidence
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0candidates include NAD(P)H NAD P H oxidase or a dysfunction eNOS 44 since each of the systems was up-regulated in diabetes
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0stress as indexed by normalization of the renal expression of p47phox renal hydrogen peroxide production and plasma LPO
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox-induced2.5Prominent among these may be p47phox-induced activation of NAD(P)H NAD P H oxidase-dependent O 2 -generation
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS-induced2.5of NAD(P)H NAD P H oxidase-dependent O 2 -generation and eNOS-induced NO generation leading to the formation of oxidative and nitrosative
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0suggest that co-expression of NAD(P)H NAD P H oxidase and eNOS leading to increased nitro-oxidative stress could be one such factor
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0Intervention studies to block NAD(P)H NAD P H oxidase or eNOS are needed to address this hypothesis directly
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0Light micrographs illustrating immunostaining for NAD(P)H NAD P H oxidase p47phox in glomerulus ( a c e g and inner medulla
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0Western blot for p47phox using whole kidney homogenate analyzed by densitometry (mean mean SEM
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox3.0A prominent band for p47phox is observed at 47 kD
7872NOS1nitric oxide synthase 1 (neuronal)nNOS3.2Light micrographs illustrating immunostaining for neuronal nitric oxide synthase (nNOS) nNOS and endothelial nitric oxide synthase (eNOS) eNOS
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0oxide synthase (nNOS) nNOS and endothelial nitric oxide synthase (eNOS) eNOS
7872NOS1nitric oxide synthase 1 (neuronal)nNOS3.2Immunoreactivity for nNOS is observed in macula densa and that for eNOS is
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0for nNOS is observed in macula densa and that for eNOS is in endothelial cells in glomerulus and renal artery
7872NOS1nitric oxide synthase 1 (neuronal)nNOS3.2Magnification 280 for nNOS 240 for eNOS in glomerulus and 180 for eNOS in
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0Magnification 280 for nNOS 240 for eNOS in glomerulus and 180 for eNOS in renal artery
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0for nNOS 240 for eNOS in glomerulus and 180 for eNOS in renal artery
7872NOS1nitric oxide synthase 1 (neuronal)nNOS3.2Western blot studies of nNOS expression in the whole kidney homogenates showing a specific band
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0Western blot of eNOS expression in the whole kidney homogenates were quantified by densitometry
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS4.0A specific band for eNOS was observed at 133 kD * P _lt_ 0.05 vs
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)nitric oxide synthase1.0oxidative stress and nitric oxide synthase in rat diabetic nephropathy: effects of acei and arb.
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)ang ii1.0background angiotensin ii ang ii can up regulate nicotinamide adenine dinucleotide phosphate [nad p h] oxidase whose product superoxide anion o 2 can interact with nitric oxide no to form peroxynitrite onoo .
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)angiotensin ii1.0background angiotensin ii ang ii can up regulate nicotinamide adenine dinucleotide phosphate [nad p h] oxidase whose product superoxide anion o 2 can interact with nitric oxide no to form peroxynitrite onoo .
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)ang ii1.0we tested the hypothesis that ang ii subtype 1 at 1 receptor activation enhances oxidative stress and nitrotyrosine deposition in the kidneys of rats with diabetes mellitus dm .
2707ACEangiotensin I converting enzyme (peptidyl-dipeptidase A) 1angiotensin converting enzyme1.0methods after two weeks of streptozotocin induced dm rats received either no treatment an angiotensin converting enzyme inhibitor acei or an angiotensin receptor blocker arb for two weeks.
7872NOS1nitric oxide synthase 1 (neuronal)neuronal nitric oxide synthase1.0at four weeks renal expression of the p47phox component of nad p h oxidase endothelial nitric oxide synthase enos neuronal nitric oxide synthase nnos and nitrotyrosine were evaluated by western blot and immunohistochemistry and related to plasma lipid peroxidation products lpo hydrogen peroxide production in the kidney and 24 hour protein exc
7876NOS3nitric oxide synthase 3 (endothelial cell)endothelial nitric oxide synthase1.0at four weeks renal expression of the p47phox component of nad p h oxidase endothelial nitric oxide synthase enos neuronal nitric oxide synthase nnos and nitrotyrosine were evaluated by western blot and immunohistochemistry and related to plasma lipid peroxidation products lpo hydrogen peroxide production i
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)angiotensin ii1.0up regulation of p47phox is seen in the kidneys of spontaneously hypertensive rat shr which is a model of angiotensin ii subtype 1 at 1 receptor dependent oxidative stress abstract; chabrashvili et al j am soc nephrol 10:343a 1999 23 .
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)ang ii1.0in vascular smooth muscle cells p47phox is linked to ang ii dependent jak/stat signaling events that underlie proliferation 24 .
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)ang ii1.0therefore our initial studies have focused on the p47phox component although in vasculature angiotensin ii ang ii also up regulates p22phox 25 and p67phox 26 .
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)angiotensin ii1.0therefore our initial studies have focused on the p47phox component although in vasculature angiotensin ii ang ii also up regulates p22phox 25 and p67phox 26 .
11765TGFAtransforming growth factor, alphatransforming growth factor1.0the activation of nad p h oxidase in diabetes mellitus dm is postulated to suppress the action of no 3 7 8 to increase the expression of the mrna for transforming growth factor beta1 tgf beta1 and fibronectin in the glomerulus 4 5 to decrease the expression of matrix metalloproteinases and to increase the expression of the tissue inhibitor of metalloproteinases in the kidne
11766TGFB1transforming growth factor, beta 1transforming growth factor beta11.0the activation of nad p h oxidase in diabetes mellitus dm is postulated to suppress the action of no 3 7 8 to increase the expression of the mrna for transforming growth factor beta1 tgf beta1 and fibronectin in the glomerulus 4 5 to decrease the expression of matrix metalloproteinases and to increase the expression of the tissue inhibitor of metalloproteinases in the kidney 2 6
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase1.0onse is absent in arterioles microdissected from kidneys of rabbits with early streptozotocin induced dm but a partial response can be restored by a membrane permeable nitroxide tempol that acts as a superoxide dismutase sod mimetic 9 .
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)nitric oxide synthase1.0ile these data implicate the potential importance of oxidative stress in functional no deficiency in diabetic nephropathy the sources of o 2 remain unclear since other oxidases including constitutive nitric oxide synthase nos lipooxygenase and xanthine oxidase all can contribute to oxidative stress in other models of hypertension or renal pathology 27 28 29 .
12805XDHxanthine dehydrogenasexanthine oxidase1.0tance of oxidative stress in functional no deficiency in diabetic nephropathy the sources of o 2 remain unclear since other oxidases including constitutive nitric oxide synthase nos lipooxygenase and xanthine oxidase all can contribute to oxidative stress in other models of hypertension or renal pathology 27 28 29 .
2707ACEangiotensin I converting enzyme (peptidyl-dipeptidase A) 1angiotensin converting enzyme1.0angiotensin converting enzyme inhibitors aceis 30 31 32 and angiotensin receptor blockers arbs 33 34 have beneficial effects on proteinuria in human diabetic nephropathy.
399ALBalbuminalbumin1.0measurement of lipid peroxidation hydrogen peroxide creatinine albumin and glucose the lipid peroxidation products in plasma were measured by thiobarbituric acid method 37 .
399ALBalbuminalbumin1.0the albumin in urine was quantified by enzyme linked immunosorbent assay elisa kit panaform lab. kumamoto japan .
7872NOS1nitric oxide synthase 1 (neuronal)neuronal nitric oxide synthase1.0th 5% nonfat dried milk in tris buffered saline containing 0.1% tween 20 tbst for 30 minutes following overnight incubation with monoclonal antibody for p47phox endothelial nitric oxide synthase enos neuronal nitric oxide synthase nnos; transduction laboratories lexington ky usa and nitrotyrosine upstate technology lake placid ny usa in a 1:1000 dilution.
7876NOS3nitric oxide synthase 3 (endothelial cell)endothelial nitric oxide synthase1.0the membranes were incubated with 5% nonfat dried milk in tris buffered saline containing 0.1% tween 20 tbst for 30 minutes following overnight incubation with monoclonal antibody for p47phox endothelial nitric oxide synthase enos neuronal nitric oxide synthase nnos; transduction laboratories lexington ky usa and nitrotyrosine upstate technology lake placid ny usa in a 1:1000 dilution.
399ALBalbuminalbumin1.0diabetic animals have a substantial increase in renal albumin excretion which was reduced to values not significantly different from control animals by the acei and the arb.
399ALBalbuminalbumin1.0renal albumin excretion renal albumin excretion was used as a marker for early diabetic nephropathy.
399ALBalbuminalbumin1.0albumin excretion was elevated significantly in rats with dm at four weeks after induction of diabetes table 1 .
399ALBalbuminalbumin1.0both the acei and the arb reduced renal albumin excretion significantly in dm.
14874NOX5NADPH oxidase, EF-hand calcium binding domain 5nadph oxidase1.0recently enhanced gp91phox nadph oxidase and enos expression in aorta have been demonstrated in the early stage of streptozotocin induced diabetic rats 44 supporting our findings of oxidative stress in the kidney of diabetic rats.
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)angiotensin ii1.0angiotensin ii stimulated nad p h oxidase activity and expression of p22phox and p67phox in vsmcs 25 26 42 .
6081INSinsulininsulin1.0in our model of insulinogenic diabetes without insulin replacement no increase in nnos protein expression in the kidney was detected nor was evidence of glomerular hyperfiltration as assessed indirectly from 24 hour creatinine clearance.
399ALBalbuminalbumin1.0renal albumin excretion angiotensin converting enzyme inhibitors and arbs reduce albumin excretion in patients with incipient or overt diabetic nephropathy 33 53 54 .
2707ACEangiotensin I converting enzyme (peptidyl-dipeptidase A) 1angiotensin converting enzyme1.0renal albumin excretion angiotensin converting enzyme inhibitors and arbs reduce albumin excretion in patients with incipient or overt diabetic nephropathy 33 53 54 .
7872NOS1nitric oxide synthase 1 (neuronal)neuronal nitric oxide synthase1.0light micrographs illustrating immunostaining for neuronal nitric oxide synthase nnos and endothelial nitric oxide synthase enos .
7876NOS3nitric oxide synthase 3 (endothelial cell)endothelial nitric oxide synthase1.0light micrographs illustrating immunostaining for neuronal nitric oxide synthase nnos and endothelial nitric oxide synthase enos .
399ALBalbuminalbumin1.0albumin excretion in control rats and over four weeks of diabetes mellitus alone or with two weeks of quinapril or candesartan administration weeks 2 4 .
2707ACEangiotensin I converting enzyme (peptidyl-dipeptidase A) 1angiotensin converting enzyme1.0table 1 effect of angiotensin converting enzyme inhibitor acei and angiotensin receptor blocker arb treatment on physiological and biochemical parameters in diabetes mellitus.
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)nitric oxide synthase1.0|reactive oxygen species|receptor angiotensin type 1|receptors angiotensin|tetrahydroisoquinolines|tetrazoles|nitric oxide|superoxides|candesartan|3 nitrotyrosine|tyrosine|hydrogen peroxide|quinapril|nitric oxide synthase|nitric oxide synthase type i|nitric oxide synthase type iii|nos1 protein rat|nos3 protein rat|nadph oxidase|neutrophil cytosolic factor 1|
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)nitric oxide synthase1.0|nitric oxide synthase type i|nitric oxide synthase type iii|nos1 protein rat|nos3 protein rat|nadph oxidase|neutrophil cytosolic factor 1|
2707ACEangiotensin I converting enzyme (peptidyl-dipeptidase A) 1angiotensin converting enzyme1.0angiotensin converting enzyme inhibitors|antihypertensive agents|benzimidazoles|isoquinolines|phosphoproteins|reactive oxygen species|receptor angiotensin type 1|receptors angiotensin|tetrahydroisoquinolines|tetrazoles|nitric oxi