)| PMID |
11812764 ( ) |
|---|---|
| Title | Vascular NADH oxidase is involved in impaired endothelium-dependent vasodilation in OLETF rats, a model of type 2 diabetes. |
| Abstract | Superoxide anion can modulate vascular smooth muscle tone and is potentially involved in diabetic vascular complications. The present study was undertaken to characterize both vascular production and the enzymatic source of superoxide anion in type 2 diabetic rats. In the thoracic aorta of OLETF rats, endothelium-dependent relaxation was markedly attenuated compared with that of control (LETO) rats in association with a significant increase in superoxide production (2,421.39 +/- 407.01 nmol x min(-1) x mg(-1)). The increased production of superoxide anion was significantly attenuated by diphenyleneiodonium (DPI; 10 micromol/l), an inhibitor of NAD(P)H oxidase. The production of superoxide anion in response to NADH as a substrate was markedly increased in the vascular homogenates, but NADPH, arachidonic acid, xanthine, and succinate produced only small increases in chemiluminescence. In line with these results, studies using various enzyme inhibitors, such as DPI, allopurinol, rotenone, N(G)-monomethyl-L-arginine, and indomethacin, suggest that the predominant source of superoxide anion in vascular particulate fraction is NADH-dependent membrane-bound oxidase. Furthermore, the expression of p22phox, a major component of vascular NAD(P)H oxidase, was markedly increased in the aorta from OLETF rats compared with that of LETO rats. These findings suggest that upregulated expression of p22phox mRNA and enhanced NADH oxidase activity contribute to the impaired endothelium-dependent vasodilation in OLETF rats. Pusan National University, Pusan, South Korea. |
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 |
|---|---|---|---|---|
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 20 | p22phox | p22phox-mediated | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 13 | SOD | superoxide dismutase | |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | 11 | endothelial nitric oxide synthase | eNOS | |
| 12805 | XDH | xanthine dehydrogenase | 5 | xanthine oxidase | |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | 3 | cytochrome b | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 3 | gp91phox | |
| 9393 | PRKCA | protein kinase C, alpha | 3 | protein kinase c | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 2 | nadph oxidase | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 1 | p67phox | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 1 | nitric oxide synthase | |
| 6081 | INS | insulin | 1 | insulin | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 1 | p47phox | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | Furthermore the expression of p22phox a major component of vascular NAD(P)H NAD P H oxidase |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | These findings suggest that upregulated expression of p22phox mRNA and enhanced NADH oxidase activity contribute to the impaired |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.3 | of four major subunits a membrane-associated cytochrome b 558 comprising gp91phox and p22phox and two cytosolic components p47phox and p67phox |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | major subunits a membrane-associated cytochrome b 558 comprising gp91phox and p22phox and two cytosolic components p47phox and p67phox |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 1.6 | b 558 comprising gp91phox and p22phox and two cytosolic components p47phox and p67phox |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 1.6 | comprising gp91phox and p22phox and two cytosolic components p47phox and p67phox |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | association with increased activity of NADH oxidase with enhanced vascular p22phox mRNA expression in OLETF rats suggesting the possible role of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | l in the presence or absence of superoxide dismutase (SOD; SOD 500 units/ml) units ml were recorded |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | For immunohistochemical staining of endothelial NO synthase (eNOS), eNOS after immersion fixation in acetone (4degreeC), 4degreeC aortic sections were |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | A monoclonal antibody to eNOS (Oncogene, Oncogene Boston MA was applied for 60 min followed |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | 0.1 mol/l mol l sodium acetate buffer (pH pH 5.2 eNOS immunoreactivity was made visible with diaminobenzidine solution (Vector Vector Laboratories |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | Immunoreactivity for eNOS was quantitated by Image-Pro Plus Imaging software (Media Media Cybernetics |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | some experiments diphenyleneiodinium (DPI; DPI 10 micromol/l) micromol l and SOD (500 500 units/ml) units ml were added to the samples |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | after the addition of DPI (10 10 micromol/l), micromol l SOD (500 500 units/ml), units ml allopurinol (100 100 micromol/l), micromol |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | A full-length cDNA for rat p22phox (provided provided by Kathy K Griendling was labeled with P-alpha |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | recorded in the presence (_amp_#149;, _amp_#149 or absence ( of SOD (500 500 units/ml) units ml |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | Comparison of densities of immunohistochemical stain for eNOS in aortas from LETO and OLETF rats |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | The density of eNOS staining in aortic cross sections was expressed as pixels per |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | various inhibitors such as DPI (10 10 micromol/l), micromol l SOD (500 500 units/ml), units ml allopurinol (100 100 micromol/l), micromol |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | The expression of p22phox mRNA in the thoracic aorta derived from LETO and OLETF |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | The top panel shows a representative Northern blot with the p22phox mRNA band at 0.8 kb |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | ACh in OLETF rats was significantly enhanced by pretreatment with SOD (500 500 units/ml), units ml suggesting the role of superoxide |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | Immunohistochemistry for eNOS |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | Immunohistochemical results showed no difference in the density of eNOS staining between aortas from LETO and OLETF rats ( Fig.2 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | several interventions such as DPI (10 10 micromol/l), micromol l SOD (500 500 units/ml), units ml allopurinol (100 100 micromol/l), micromol |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | In addition treatment with SOD at high concentration was more effective in reducing the NADH-stimulated |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | Expression of vascular p22phox mRNA |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | Because p22phox one of the membrane-associated components of vascular NAD(P)H NAD P |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | and functional in the vasculature ( 24 -27 we investigated p22phox mRNA expression in LETO and OLETF rats by Northern blot |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | As shown in Fig 6 the level of p22phox mRNA expression was greater in OLETF than in LETO rats |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | These data suggest that the upregulated expression of p22phox mRNA may be responsible for the overproduction of superoxide anion |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | impaired endothelium-dependent vasodilation that was partially normalized by pretreatment with SOD ( Fig 1 |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | Furthermore there was no significant difference in eNOS expression in the aortic endothelium of OLETF and control rats |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | OLETF rats was partially inhibited by DPI and blocked by SOD ( Fig 5 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | In particular p22phox forming cytochrome b 558 by making a complex with gp91phox |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.3 | p22phox forming cytochrome b 558 by making a complex with gp91phox is integral for the oxidase activation to produce superoxide anion |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox-mediated | 0.8 | In a previous study p22phox-mediated expression of cytochrome b 558 in the absence of gp91phox |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.3 | p22phox-mediated expression of cytochrome b 558 in the absence of gp91phox was investigated ( 32 the importance of p22phox was increased |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | absence of gp91phox was investigated ( 32 the importance of p22phox was increased |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | by NADH oxidase is influenced by increased mRNA expression of p22phox in diabetic rats |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | After Northern blot analysis we found that p22phox mRNA expression was markedly increased in diabetic vessels ( Fig |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | the consequence of either stimulated NADH oxidase activity or elevated p22phox mRNA expression or both |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | increased NADH oxidase-dependent superoxide production via enhanced vascular expression of p22phox |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 6.1 | K Griendling from Emory University for her generous gift of p22phox cDNA |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | ACh acetylcholine DPI diphenyleneiodonium eNOS endothelial nitric oxide synthase L -NMMA N -monomethyl-L -arginine NO |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | NO nitric oxide ROS reactive oxygen species SNP sodium nitroprusside SOD superoxide dismutase |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | among various sources for ros such as nad p h oxidase cyclooxygenase xanthine oxidase nitric oxide no synthase and mitochondrial electron transport nad p h oxidase has been considered to be a major source of ros in the vasculature 16 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | vascular nad p h oxidase is similar in structure to the neutrophil nadph oxidase which consists of four major subunits: a membrane associated cytochrome b 558 comprising gp91phox and p22phox and two cytosolic components p47phox and p67phox. |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | vascular nad p h oxidase is similar in structure to the neutrophil nadph oxidase which consists of four major subunits: a membrane associated cytochrome b 558 comprising gp91phox and p22phox and two cytosolic components p47phox and p67phox. |
| 6081 | INS | insulin | insulin | 1.0 | this animal model displays some characteristic features such as late onset of hyperglycemia after 18 weeks of age hyperinsulinemia obesity and insulin deficiency. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | ontracted with u46619 30 nmol/l and after a plateau had been reached the relaxations to acetylcholine ach; 10 to 10 mol/l or sodium nitroprusside snp; 3 x 10 to 10 mol/l in the presence or absence of superoxide dismutase sod; 500 units/ml were recorded. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | the amount of superoxide anion was calculated by comparison with a standard curve generated from known quantities of xanthine and xanthine oxidase 23 . |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | however stimulated nadh oxidase activity was insensitive to allopurinol inhibitor of xanthine oxidase rotenone inhibitor of mitochondrial electron transport chain l nmma nitric oxide synthase inhibitor and indomethacin cyclooxygenase inhibitor fig.5 . |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | however stimulated nadh oxidase activity was insensitive to allopurinol inhibitor of xanthine oxidase rotenone inhibitor of mitochondrial electron transport chain l nmma nitric oxide synthase inhibitor and indomethacin cyclooxygenase inhibitor fig.5 . |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | from this result we noted that production of superoxide anion in diabetic vessels is achieved via the flavoprotein containing enzymes such as nad p h oxidase xanthine oxidase cyclooxygenase and no synthase. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | these findings excluded an important role for cyclooxygenase xanthine oxidase no synthase and mitochondrial electron transport as a potential mechanism for superoxide production indicating that the targeted inhibition of elevated superoxide production by dpi is nadh oxidase. |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | in particular p22phox forming cytochrome b 558 by making a complex with gp91phox is integral for the oxidase activation to produce superoxide anion. |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | in a previous study p22phox mediated expression of cytochrome b 558 in the absence of gp91phox was investigated 32 ; the importance of p22phox was increased. |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | koya and king 33 have shown that high glucose levels activate protein kinase c in various vascular cells. |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | furthermore it has been reported that high glucose levels stimulate the production of ros through protein kinase c dependent activation of nad p h oxidase in vascular smooth muscle cells 34 . |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | according to the previous reports protein kinase c may play an important role in the process of nad p h oxidase activation; however further studies are required to elucidate the precise molecular mechanisms involved in the activation of nad p h oxida |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | endothelial nitric oxide synthase | 1.0 | ach acetylcholine; dpi diphenyleneiodonium; enos endothelial nitric oxide synthase; l nmma n monomethyl l arginine; no nitric oxide; ros reactive oxygen species; snp sodium nitroprusside; sod superoxide dismutase. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | ach acetylcholine; dpi diphenyleneiodonium; enos endothelial nitric oxide synthase; l nmma n monomethyl l arginine; no nitric oxide; ros reactive oxygen species; snp sodium nitroprusside; sod superoxide dismutase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | me complexes|phosphoproteins|rna messenger|superoxides|oxidoreductases|nitric oxide synthase|nitric oxide synthase type iii|nos3 protein rat|nadh oxidase|nadh nadph oxidoreductases|cyba protein human|nadph oxidase|nadph dehydrogenase| |