)| PMID |
15840036 ( ) |
|---|---|
| Title | Effects of NADPH oxidase inhibitor in diabetic nephropathy. |
| Abstract | BACKGROUND: We used apocynin to test the hypothesis that superoxide anion (O(-) (2)) from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase underlies the development of diabetic nephropathy in the rat. METHODS: Rats received apocynin (16 mg/kg/day) from 2 to 8 weeks after inducing diabetes mellitus (DM) with streptozotocin. RESULTS: DM increased excretion of hydrogen peroxide (H(2)O(2)), lipid peroxidation products (LPO), nitric oxide products (NOx), and protein. The kidneys of rats with DM had increased expression of p47phox and gp91phox and endothelial nitric oxide synthase (eNOS), and increased mesangial matrix with expression of fibronectin and collagen I. Apocynin prevented the increase in excretion of H(2)O(2), LPO, and protein in diabetic rats, increased renal NOx generation, and prevented the increased renal expression of gp91phox and the membrane fraction of p47phox, and reverted the mesangial matrix expansion. CONCLUSION: Activation of NADPH oxidase with translocation of p47phox to the membrane underlies the oxidative stress and limited NO generation, despite enhanced eNOS expression in a model of diabetic nephropathy. Apocynin prevents these changes and the associated proteinuria. Japan. |
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 |
|---|---|---|---|---|
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 29 | p47phox | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 27 | nadph oxidase | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 20 | gp91phox | |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | 17 | endothelial nitric oxide synthase | eNOS | |
| 2197 | COL1A1 | collagen, type I, alpha 1 | 8 | collagen | collagen-induced | collagen i | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 6 | p22phox | |
| 2898 | DLD | dihydrolipoamide dehydrogenase | 5 | diaphorase | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 4 | TNF-alpha | tnf alpha | |
| 5992 | IL1B | interleukin 1, beta | 4 | IL-1 | il 1 | |
| 1516 | CAT | catalase | 4 | catalase | |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | 4 | NOS | |
| 4823 | HBA1 | hemoglobin, alpha 1 | 3 | HbA | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 3 | angiotensin ii | ang ii | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 2 | p67phox | |
| 5962 | IL10 | interleukin 10 | 2 | IL-10 | il 10 | |
| 6014 | IL4 | interleukin 4 | 2 | IL-4 | il 4 | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 2 | SOD | superoxide dismutase | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 1 | nitric oxide synthase | |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 1 | Rac | |
| 12805 | XDH | xanthine dehydrogenase | 1 | xanthine oxidase | |
| 399 | ALB | albumin | 1 | albumin | |
| 9393 | PRKCA | protein kinase C, alpha | 1 | protein kinase c | |
| 5438 | IFNG | interferon, gamma | 1 | IFN-gamma | |
| 7662 | NCF4 | neutrophil cytosolic factor 4, 40kDa | 1 | p40phox | |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | 1 | angiotensin converting enzyme | |
| 7889 | NOX1 | NADPH oxidase 1 | 1 | Nox1 | |
| 7891 | NOX4 | NADPH oxidase 4 | 1 | Nox4 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | The kidneys of rats with DM had increased expression of p47phox and gp91phox and endothelial nitric oxide synthase (eNOS), eNOS and |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | of rats with DM had increased expression of p47phox and gp91phox and endothelial nitric oxide synthase (eNOS), eNOS and increased mesangial |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | of p47phox and gp91phox and endothelial nitric oxide synthase (eNOS), eNOS and increased mesangial matrix with expression of fibronectin and collagen |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen | 0.3 | eNOS and increased mesangial matrix with expression of fibronectin and collagen I Apocynin prevented the increase in excretion of H 2 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | renal NOx generation and prevented the increased renal expression of gp91phox and the membrane fraction of p47phox and reverted the mesangial |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | increased renal expression of gp91phox and the membrane fraction of p47phox and reverted the mesangial matrix expansion |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | Conclusion Activation of NADPH oxidase with translocation of p47phox to the membrane underlies the oxidative stress and limited NO |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | underlies the oxidative stress and limited NO generation despite enhanced eNOS expression in a model of diabetic nephropathy |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | and the antioxidant defense system that includes superoxide dismutase (SOD) SOD and peroxidases determines the degree of oxidative stress |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | The phagocyte NADPH oxidase consists of membrane-bound subunits (gp91phox gp91phox and p22phox and cytosolic subunits (p47phox, p47phox p40phox p67phox and |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | membrane-bound subunits (gp91phox gp91phox and p22phox and cytosolic subunits (p47phox, p47phox p40phox p67phox and Rac 3 |
| 7662 | NCF4 | neutrophil cytosolic factor 4, 40kDa | p40phox | 2.2 | subunits (gp91phox gp91phox and p22phox and cytosolic subunits (p47phox, p47phox p40phox p67phox and Rac 3 |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 2.2 | (gp91phox gp91phox and p22phox and cytosolic subunits (p47phox, p47phox p40phox p67phox and Rac 3 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 0.1 | phagocyte NADPH oxidase consists of membrane-bound subunits (gp91phox gp91phox and p22phox and cytosolic subunits (p47phox, p47phox p40phox p67phox and Rac 3 |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Rac | 0.1 | and p22phox and cytosolic subunits (p47phox, p47phox p40phox p67phox and Rac 3 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | When activated p47phox is phosphorylated and the cytosolic components translocate to the membrane |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | Moreover there are homologues of the gp91phox subunit that include Nox1 which is expressed in vascular smooth |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 0.9 | Moreover there are homologues of the gp91phox subunit that include Nox1 which is expressed in vascular smooth muscle cells (VSMCs), VSMCs |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 0.9 | is expressed in vascular smooth muscle cells (VSMCs), VSMCs and Nox4 which is expressed in the kidney and blood vessels 5 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | It inhibits NADPH oxidase by impeding the assembly of p47phox and p67phox subunits within the membrane NADPH oxidase complex 7 |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 2.2 | inhibits NADPH oxidase by impeding the assembly of p47phox and p67phox subunits within the membrane NADPH oxidase complex 7 8 |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen-induced | 0.3 | Administration of apocynin to rats with collagen-induced arthritis prevents joint destruction 9 |
| 4823 | HBA1 | hemoglobin, alpha 1 | HbA | 0.3 | HbA 1c was measured with the DCA 2000 plus system (Bayer |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | (TBST), TBST followed by overnight incubation with monoclonal antibodies recognizing p47phox gp91phox and p22phox 6 at 1 1000 dilutions and a |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | TBST followed by overnight incubation with monoclonal antibodies recognizing p47phox gp91phox and p22phox 6 at 1 1000 dilutions and a polyclonal |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | and a polyclonal antibody recognizing endothelial nitric oxide synthase (eNOS; eNOS Santa Cruz Biotechnology Inc. Santa Cruz CA USA at a |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 0.1 | by overnight incubation with monoclonal antibodies recognizing p47phox gp91phox and p22phox 6 at 1 1000 dilutions and a polyclonal antibody recognizing |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | antibodies (1:1000 1 1000 dilutions Dako Glostrup Denmark to detect p47phox gp91phox and p22phox or eNOS respectively |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | (1:1000 1 1000 dilutions Dako Glostrup Denmark to detect p47phox gp91phox and p22phox or eNOS respectively |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | Dako Glostrup Denmark to detect p47phox gp91phox and p22phox or eNOS respectively |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 0.2 | 1000 dilutions Dako Glostrup Denmark to detect p47phox gp91phox and p22phox or eNOS respectively |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | They were incubated overnight with polyclonal antibodies recognizing p47phox gp91phox 6 and eNOS (Santa Santa Cruz Biotechnology type I |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | They were incubated overnight with polyclonal antibodies recognizing p47phox gp91phox 6 and eNOS (Santa Santa Cruz Biotechnology type I collagen |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | incubated overnight with polyclonal antibodies recognizing p47phox gp91phox 6 and eNOS (Santa Santa Cruz Biotechnology type I collagen and fibronectin (Chemicon |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen | 0.3 | gp91phox 6 and eNOS (Santa Santa Cruz Biotechnology type I collagen and fibronectin (Chemicon Chemicon International Inc. Temecula CA USA at |
| 4823 | HBA1 | hemoglobin, alpha 1 | HbA | 0.3 | Physiologic data As shown in Table 1 blood glucose and HbA 1c were significantly higher in diabetic rats than in controls |
| 4823 | HBA1 | hemoglobin, alpha 1 | HbA | 0.3 | Diabetic rats administered apocynin had higher values for HbA 1c compared to those with DM at 4 weeks but |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | Expression of NADPH oxidase subunits The p47phox component of NADPH oxidase was expressed in glomerular cells and |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | Apocynin treatment reduced p47phox staining in diabetic rats Figure 1 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | Western blotting confirmed that p47phox protein was increased significantly in DM rats at 8 weeks |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | Apocynin significantly reduced p47phox expression in the membrane fractions of the kidney (0.21 0.21 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | The ratio of p47phox expression in membranes cytosol was 1.10 0.07 in control rats |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | This indicates that apocynin inhibited membrane translocation of p47phox |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | The gp91phox was expressed in glomerular cells and distal tubules |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | Apocynin reduced the expression of gp91phox in the glomeruli Figure 1 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | membrane fraction of the kidney showed a specific band for gp91phox that was increased in DM rats (0.30 0.30 0.02 vs |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | Apocynin prevented the significant increase in the membrane fraction of gp91phox protein expression of DM rats (0.25 0.25 0.02 NS vs |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 0.0 | The expression of p22phox in the membrane fraction was unchanged in DM rats compared |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | Expression of eNOS and nitrite production in the kidney Immunohistochemical analysis showed that |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | in the kidney Immunohistochemical analysis showed that the expression of eNOS in endothelial cells of the renal artery was increased in |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | Western blot analysis confirmed an increase in eNOS expression in DM rats (0.28 0.28 0.01 vs 0.19 0.01 |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | Treatment with apocynin did not change eNOS expression in DM rats (0.32 0.32 0.01 NS vs DM |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | diaphorase histochemistry was used as a descriptive method to detect NOS expression 22 26 27 and DAF-2 fluorescence to detect NO |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | These methods indicated that NO production from NOS in proximal tubules and endothelial cells of the renal vasculature |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen | 0.3 | Immunohistochemistry demonstrated increased mesangial expression of fibronectin and type I collagen in DM rat mesangial cells |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | with apocynin in diabetic rats prevents the membrane translocation of p47phox and the increased expression of gp91phox in the kidney and |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | the membrane translocation of p47phox and the increased expression of gp91phox in the kidney and prevents oxidative stress proteinuria and glomerulopathy |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | both by expression of the subunits and by phosphorylation of p47phox following stimulation by agents such as angiotensin II IL-1 beta |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.0 | of p47phox following stimulation by agents such as angiotensin II IL-1 beta and TNF-alpha 28 29 30 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 0.5 | stimulation by agents such as angiotensin II IL-1 beta and TNF-alpha 28 29 30 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | by Western blotting and immunohistochemistry that the renal expression of p47phox and gp91phox were enhanced in diabetic rats |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | blotting and immunohistochemistry that the renal expression of p47phox and gp91phox were enhanced in diabetic rats |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | This is consistent with recent reports that p47phox and gp91phox are up-regulated in the kidneys of salt loaded |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | This is consistent with recent reports that p47phox and gp91phox are up-regulated in the kidneys of salt loaded rats 31 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | Apocynin reduced the expression of p47phox in the membrane but not in the cytosolic fraction indicating |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | the cytosolic fraction indicating that it inhibited translocation of the p47phox subunit to the membrane fraction |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | The expression of another membrane-bound subunit gp91phox was increased in the kidney of DM rats and this |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 0.0 | Another critical membrane subunit p22phox did not change significantly with diabetes and was not altered |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | by apocynin may be suppression of translocation of the cytosolic p47phox component to the membrane fraction with associated suppression of its |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | to the membrane fraction with associated suppression of its anchor gp91phox where it forms a molecular cluster to activate NADPH oxidase |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | Apocynin after cellular uptake and peroxidation prevents serine phosphorylation of p47phox and blocks its association with gp91phox |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | prevents serine phosphorylation of p47phox and blocks its association with gp91phox |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | NO has been ascribed both to an increased expression of eNOS 2 38 40 which was confirmed in this study and |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | was confirmed in this study and to activation of neuronal NOS expressed in the macula densa 40 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | diaphorase histochemical methods were used to locate the source of NOS and the activity of NO in this study |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | While apocynin did not further modify eNOS expression it enhanced renal NOx generation and enhanced NO bioactivity |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | It may have protected eNOS from the effects of oxidation of tetrahydrobiopterin which can uncouple |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | from the effects of oxidation of tetrahydrobiopterin which can uncouple eNOS from NO synthesis and perpetuate O -2 generation 42 43 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 0.5 | inhibits the neutrophil oxidative burst and generation of cytokines including TNF-alpha IL-1 beta IFN-gamma IL-4 and IL-10 9 36 46 |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.0 | the neutrophil oxidative burst and generation of cytokines including TNF-alpha IL-1 beta IFN-gamma IL-4 and IL-10 9 36 46 |
| 5438 | IFNG | interferon, gamma | IFN-gamma | 0.8 | oxidative burst and generation of cytokines including TNF-alpha IL-1 beta IFN-gamma IL-4 and IL-10 9 36 46 |
| 6014 | IL4 | interleukin 4 | IL-4 | 1.0 | burst and generation of cytokines including TNF-alpha IL-1 beta IFN-gamma IL-4 and IL-10 9 36 46 |
| 5962 | IL10 | interleukin 10 | IL-10 | 1.0 | generation of cytokines including TNF-alpha IL-1 beta IFN-gamma IL-4 and IL-10 9 36 46 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | Apocynin did prevent the DM-induced increases in renal expression of gp91phox membrane-associated p47phox H 2 O 2 excretion glomerular mesangial expansion |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | prevent the DM-induced increases in renal expression of gp91phox membrane-associated p47phox H 2 O 2 excretion glomerular mesangial expansion and mesangial |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen | 0.3 | excretion glomerular mesangial expansion and mesangial expression of fibronectin and collagen I and expression of p47phox in podocytes and of H |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | mesangial expression of fibronectin and collagen I and expression of p47phox in podocytes and of H 2 O 2 generation by |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | For example preventing activation of p47phox in podocytes may limit local oxidative stress |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | oxidase in a model of diabetic nephropathy with translocation of p47phox to the membrane underlies the generation of peroxides and limits |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | Light micrographs illustrating immunostaining for NADPH oxidase p47phox ( A to C and gp91phox ( D to F |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | immunostaining for NADPH oxidase p47phox ( A to C and gp91phox ( D to F in the kidney immunostaining for eNOS |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | gp91phox ( D to F in the kidney immunostaining for eNOS in the renal artery ( G to I periodic acid-Schiff |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen | 0.3 | immunostaining for fibronectin ( M to O and type I collagen ( P to R |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 3.0 | Western blot analysis of NADPH oxidase p47phox in membrane and cytosolic fractions at 8 weeks |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.5 | Western blot analysis of NADPH oxidase gp91phox and p22phox in the membrane fraction at 8 weeks |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 0.1 | Western blot analysis of NADPH oxidase gp91phox and p22phox in the membrane fraction at 8 weeks |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.5 | Western blot analysis of eNOS in whole kidney homogenate at 8 weeks |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | effects of nadph oxidase inhibitor in diabetic nephropathy. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | background we used apocynin to test the hypothesis that superoxide anion o 2 from nicotinamide adenine dinucleotide phosphate nadph oxidase underlies the development of diabetic nephropathy in the rat. |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen i | 1.0 | the kidneys of rats with dm had increased expression of p47phox and gp91phox and endothelial nitric oxide synthase enos and increased mesangial matrix with expression of fibronectin and collagen i. apocynin prevented the increase in excretion of h 2 o 2 lpo and protein in diabetic rats increased renal nox generation and prevented the increased renal expression of gp91phox and the membrane frac |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | endothelial nitric oxide synthase | 1.0 | the kidneys of rats with dm had increased expression of p47phox and gp91phox and endothelial nitric oxide synthase enos and increased mesangial matrix with expression of fibronectin and collagen i. apocynin prevented the increase in excretion of h 2 o 2 lpo and protein in diabetic rats increased renal nox generat |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | conclusion activation of nadph oxidase with translocation of p47phox to the membrane underlies the oxidative stress and limited no generation despite enhanced enos expression in a model of diabetic nephropathy. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | keywords: nadph oxidase nitric oxide synthase proteinuria diabetic nephropathy apocynin |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | keywords: nadph oxidase nitric oxide synthase proteinuria diabetic nephropathy apocynin |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | the balance between the production of reactive oxygen species ros notably superoxide anion o 2 and hydrogen peroxide h 2 o 2 and the antioxidant defense system that includes superoxide dismutase sod and peroxidases determines the degree of oxidative stress. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | an important source of ros production is nicotinamide adenine dinucleotide phosphate nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the phagocyte nadph oxidase consists of membrane bound subunits gp91phox and p22phox and cytosolic subunits p47phox p40phox p67phox and rac 3 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | for example nadph oxidase is assembled primarily on intracellular organelles in endothelial cells 4 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in the kidney nadph oxidase components are expressed abundantly in the renal vessels and in the glomerular mesangial and podocyte cells the macula densa and the thick ascending limb distal tubule and collecting ducts 6 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the renal expression of nadph oxidase is enhanced in rat diabetic nephropathy. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in this model an angiotensin converting enzyme inhibitor acei or an angiotensin receptor blocker arb suppresses renal nadph oxidase renal ros generation and microalbuminuria 2 . |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | angiotensin converting enzyme | 1.0 | in this model an angiotensin converting enzyme inhibitor acei or an angiotensin receptor blocker arb suppresses renal nadph oxidase renal ros generation and microalbuminuria 2 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | thus we tested the hypothesis that administration of the nadph oxidase inhibitor apocynin to diabetic rats will reduce renal o 2 production and prevent proteinuria. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | it inhibits nadph oxidase by impeding the assembly of p47phox and p67phox subunits within the membrane nadph oxidase complex 7 8 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | we evaluated the effect of apocynin on nadph oxidase expression and examined its effect on ros generation and proteinuria in a rat model of insulinopenic diabetic nephropathy. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | this dose of apocynin 4 hydroxy 3 methoxyacetophenone was based on in vivo studies of prolonged dosing in which apocynin 4 to 100 mg/kg/day prevented nadph oxidase activation vascular superoxide o 2 production and remodeling hypertension inflammation and/or organ dysfunction in a number of models of chronic oxidative stress 10 11 12 13 14 15 . |
| 1516 | CAT | catalase | catalase | 1.0 | to confirm the specificity of dcf signal for hydrogen peroxide production isolated glomeruli from dm rat were preincubated with 5000 u/ml of catalase wako for 20 minutes and then incubated with dcfh da reagent with catalase for another 20 minutes. |
| 1516 | CAT | catalase | catalase | 1.0 | wako for 20 minutes and then incubated with dcfh da reagent with catalase for another 20 minutes. |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | endothelial nitric oxide synthase | 1.0 | d saline containing 0.1% tween 20 tbst followed by overnight incubation with monoclonal antibodies recognizing p47phox gp91phox and p22phox 6 at 1:1000 dilutions and a polyclonal antibody recognizing endothelial nitric oxide synthase enos; santa cruz biotechnology inc. santa cruz ca usa at a 1:100 dilution. |
| 2898 | DLD | dihydrolipoamide dehydrogenase | diaphorase | 1.0 | no production detected by nadph diaphorase histochemistry and daf 2 kidneys were embedded in oct compound and frozen. |
| 2898 | DLD | dihydrolipoamide dehydrogenase | diaphorase | 1.0 | to confirm the specificity of no production samples from dm rats were preincubated with 1 mmol/l n nitro l arginine methyl ester l name sigma chemical co. for 60 minutes and then nadph diaphorase or daf 2da reagents were added with 1 mmol/l l name. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | expression of nadph oxidase subunits the p47phox component of nadph oxidase was expressed in glomerular cells and distal tubules in kidneys of control rats. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | glomerular and urinary oxidative products associated with the increased nadph oxidase components in dm rats their isolated glomeruli showed increased peroxide production which was reduced by apocynin treatment figure 4 . |
| 1516 | CAT | catalase | catalase | 1.0 | the dcf signal in the glomerulus from dm rat was reduced by catalase pretreatment indicating that the signals represent hydrogen peroxide production. |
| 2898 | DLD | dihydrolipoamide dehydrogenase | diaphorase | 1.0 | nadph diaphorase histochemistry was used as a descriptive method to detect nos expression 22 26 27 and daf 2 fluorescence to detect no activity 18 23 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the main new findings of this study are that blockade of nadph oxidase with apocynin in diabetic rats prevents the membrane translocation of p47phox and the increased expression of gp91phox in the kidney and prevents oxidative stress proteinuria and glomerulopathy while |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | the activity of nadph oxidase is regulated both by expression of the subunits and by phosphorylation of p47phox following stimulation by agents such as angiotensin ii il 1 beta and tnf alpha 28 29 30 . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the activity of nadph oxidase is regulated both by expression of the subunits and by phosphorylation of p47phox following stimulation by agents such as angiotensin ii il 1 beta and tnf alpha 28 29 30 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the activity of nadph oxidase is regulated both by expression of the subunits and by phosphorylation of p47phox following stimulation by agents such as angiotensin ii il 1 beta and tnf alpha 28 29 30 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | the activity of nadph oxidase is regulated both by expression of the subunits and by phosphorylation of p47phox following stimulation by agents such as angiotensin ii il 1 beta and tnf alpha 28 29 30 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | thus a mechanism of nadph oxidase inhibition by apocynin may be suppression of translocation of the cytosolic p47phox component to the membrane fraction with associated suppression of its anchor gp91phox where it forms a molecular cl |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | cynin may be suppression of translocation of the cytosolic p47phox component to the membrane fraction with associated suppression of its anchor gp91phox where it forms a molecular cluster to activate nadph oxidase. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | this blunts nadph oxidase activation as shown in studies of neutrophils 32 and angiotensin ii ang ii stimulated vsmcs from human resistance arteries 33 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | this blunts nadph oxidase activation as shown in studies of neutrophils 32 and angiotensin ii ang ii stimulated vsmcs from human resistance arteries 33 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | this blunts nadph oxidase activation as shown in studies of neutrophils 32 and angiotensin ii ang ii stimulated vsmcs from human resistance arteries 33 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | while the primary established target for apocynin is to block assembly and activation of nadph oxidase there are secondary consequences of this in endothelial cells where xanthine oxidase expression and o 2 generation from this enzyme also is inhibited 37 . |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | while the primary established target for apocynin is to block assembly and activation of nadph oxidase there are secondary consequences of this in endothelial cells where xanthine oxidase expression and o 2 generation from this enzyme also is inhibited 37 . |
| 2898 | DLD | dihydrolipoamide dehydrogenase | diaphorase | 1.0 | fluorescent no sensitive dye and diaphorase histochemical methods were used to locate the source of nos and the activity of no in this study. |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | umatoid arthritis inflammatory bowel disease ischemic reperfusion lung injury and sepsis 9 10 15 36 46 where it inhibits the neutrophil oxidative burst and generation of cytokines including tnf alpha il 1 beta ifn gamma il 4 and il 10 9 36 46 . |
| 5962 | IL10 | interleukin 10 | il 10 | 1.0 | y bowel disease ischemic reperfusion lung injury and sepsis 9 10 15 36 46 where it inhibits the neutrophil oxidative burst and generation of cytokines including tnf alpha il 1 beta ifn gamma il 4 and il 10 9 36 46 . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | els of rheumatoid arthritis inflammatory bowel disease ischemic reperfusion lung injury and sepsis 9 10 15 36 46 where it inhibits the neutrophil oxidative burst and generation of cytokines including tnf alpha il 1 beta ifn gamma il 4 and il 10 9 36 46 . |
| 6014 | IL4 | interleukin 4 | il 4 | 1.0 | flammatory bowel disease ischemic reperfusion lung injury and sepsis 9 10 15 36 46 where it inhibits the neutrophil oxidative burst and generation of cytokines including tnf alpha il 1 beta ifn gamma il 4 and il 10 9 36 46 . |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen i | 1.0 | apocynin did prevent the dm induced increases in renal expression of gp91phox membrane associated p47phox h 2 o 2 excretion glomerular mesangial expansion and mesangial expression of fibronectin and collagen i and expression of p47phox in podocytes and of h 2 o 2 generation by isolated glomeruli. |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | thus apocynin blocks the effect of increased glucose concentration to activate protein kinase c pkc induced nadph oxidase and fibronectin secretion by peritoneal cells 48 to cause endothelial dysfunction in isolated vessels 49 and to impair contractility in cardiac myocytes 50 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | thus apocynin blocks the effect of increased glucose concentration to activate protein kinase c pkc induced nadph oxidase and fibronectin secretion by peritoneal cells 48 to cause endothelial dysfunction in isolated vessels 49 and to impair contractility in cardiac myocytes 50 . |
| 399 | ALB | albumin | albumin | 1.0 | apocynin blocks the increase in pkc o 2 generation and proliferation during incubation of mesangial cells with glycated albumin 51 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | activation of nadph oxidase in a model of diabetic nephropathy with translocation of p47phox to the membrane underlies the generation of peroxides and limits no generation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | light micrographs illustrating immunostaining for nadph oxidase p47phox a to c and gp91phox d to f in the kidney immunostaining for enos in the renal artery g to i periodic acid schiff pas stained sections of the kidney j to l and immunostaining for fibronectin m |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | western blot analysis of nadph oxidase p47phox in membrane and cytosolic fractions at 8 weeks. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | western blot analysis of nadph oxidase gp91phox and p22phox in the membrane fraction at 8 weeks. |
| 1516 | CAT | catalase | catalase | 1.0 | control a dm rat at 8 weeks b dm rat treated with apocynin c and an isolated glomerulus from dm rat pretreated with catalase d . |
| 2898 | DLD | dihydrolipoamide dehydrogenase | diaphorase | 1.0 | no production detected by nadph diaphorase histochemistry a to d and daf 2 e to h . |