)| PMID |
15777779 ( ) |
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| Title | Nitric oxide dynamics and endothelial dysfunction in type II model of genetic diabetes. |
| Abstract | Although diabetes is a major risk factor for vascular diseases, e.g., hypertension and atherosclerosis, mechanisms that underlie the "risky" aspects of diabetes remain obscure. The current study is intended to examine the notion that diabetic endothelial dysfunction stems from a heightened state of oxidative stress induced by an imbalance between vascular production and scavenging of reactive oxygen/nitrogen species. Goto-Kakizaki (GK) rats were used as a genetic animal model for non-obese type II diabetes. Nitric oxide (NO) bioavailability and O2- generation in aortic tissues of GK rats were assessed using the Griess reaction and a lucigenin-chemiluminescence-based technique, respectively. Organ chamber-based isometric tension studies revealed that aortas from GK rats had impaired relaxation responses to acetylcholine whereas a rightward shift in the dose-response curve was noticed in the endothelium-independent vasorelaxation exerted by the NO donor sodium nitroprusside. An enhancement in superoxide (O2-) production and a diminuation in NO bioavailability were evident in aortic tissues of GK diabetic rats. Immunoblotting and high-performance liquid chromatography (HPLC)-based techniques revealed, respectively, that the above inverse relationship between O2- and NO was associated with a marked increase in the protein expression of nitric oxide synthase (eNOS) and a decrease in the level of its cofactor tetrahydrobiopterin (BH4) in diabetic aortas. Endothelial denudation by rubbing or the addition of pharmacological inhibitors of eNOS (e.g. N(omega)-nitro-L-arginine methyl ester (L-NAME)), and NAD(P)H oxidase (e.g. diphenyleneiodonium, apocynin) strikingly reduced the diabetes-induced enhancement in vascular O2- production. Aortic contents of key markers of oxidative stress (isoprostane F2alpha III, protein-bound carbonyls, nitrosylated protein) in connection with the protein expression of superoxide generating enzyme NAD(P)H oxidase (e.g. p47phox, pg91phox), a major source of reactive oxygen species in vascular tissue, were elevated as a function of diabetes. In contrast, the process involves in the vascular inactivation of reactive oxygen species exemplified by the activity of CuZnSOD was reduced in this diseased state. Our studies suggest that diabetes produces a cascade of events involving production of reactive oxygen species from the NADPH oxidase leading to oxidation of BH4 and uncoupling of NOS. This promotes the oxidative inactivation of NO with subsequent formation of peroxynitrite. An alteration in the balance of these bioactive radicals in concert with a defect in the antioxidant defense counteracting mechanism may favor a heightened state of oxidative stress. This phenomenon could play a potentially important role in the pathogenesis of diabetic endothelial dysfunction. milad@hsc.kuniv.edu.kw |
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 |
|---|---|---|---|---|
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | 26 | eNOS | |
| 6081 | INS | insulin | 21 | insulin | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 19 | SOD-dependent | SODs | superoxide dismutase | |
| 19986 | CYCS | cytochrome c, somatic | 10 | cytochrome c | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 8 | nadph oxidase | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 8 | p47 | |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | 8 | NOS | |
| 12805 | XDH | xanthine dehydrogenase | 5 | xanthine oxidase | |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | 3 | MnSOD | mn superoxide dismutase | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 3 | nitric oxide synthase | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 2 | gp91 phox | |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 2 | Akt | protein kinase b | |
| 11329 | SST | somatostatin | 2 | somatostatin | |
| 9208 | POR | P450 (cytochrome) oxidoreductase | 1 | cytochrome p 450 reductase | |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | 1 | cytochrome b | |
| 12435 | TXN | thioredoxin | 1 | thioredoxin | |
| 3676 | FGF2 | fibroblast growth factor 2 (basic) | 1 | basic fibroblast growth factor | |
| 399 | ALB | albumin | 1 | serum albumin | |
| 2595 | CYP1A1 | cytochrome P450, family 1, subfamily A, polypeptide 1 | 1 | cytochrome p 450 | |
| 1516 | CAT | catalase | 1 | catalase | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 1 | angiotensin ii | |
| 2961 | DYNC1H1 | dynein, cytoplasmic 1, heavy chain 1 | 1 | P22 | |
| 336 | AGTR1 | angiotensin II receptor, type 1 | 1 | angiotensin ii receptor | |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | 1 | angiotensin converting enzyme | |
| 11765 | TGFA | transforming growth factor, alpha | 1 | transforming growth factor | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 1 | p22 phox | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | increase in the protein expression of nitric oxide synthase (eNOS) eNOS and a decrease in the level of its cofactor tetrahydrobiopterin |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | denudation by rubbing or the addition of pharmacological inhibitors of eNOS (e.g e.g |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | and the protein expression of endothelial nitric oxide synthetase (eNOS) eNOS and NAD(P)H NAD P H oxidase |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | Superoxide production was also determined using the superoxide dismutase (SOD)-inhibitable SOD -inhibitable cytochrome c assay |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | at 37 _amp_#xb0 C for 60 min with or without SOD (200 200 U/ml) U ml |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | was calculated from the difference between absorbance with or without SOD and the extinction coefficient for change of ferricytochrome c to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | Vascular SOD activity |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | min at 4 _amp_#xb0 C the supernatant was used for SOD activity testing |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD-dependent | 0.9 | The SOD-dependent inhibition of cytochrome c reduction catalyzed by xanthine oxidase was |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | One SOD unit is arbitrary defined as the amount of enzyme required |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | The CuZnSOD was differentiated from MnSOD by addition of 3 mM NaCN to eliminate the activity |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | mM NaCN to eliminate the activity of CuZnSOD from total SOD activity 2.7 |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | Western blot analysis for eNOS and protein subunits of NADPH oxidase |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | g of protein were loaded on to a 7.5% (eNOS) eNOS and 12.5% (p47 p47 phox pg91 phox Sodium dodecyl sulfate-polyacrylamide |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | loaded on to a 7.5% (eNOS) eNOS and 12.5% (p47 p47 phox pg91 phox Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) SDS-PAGE |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | in PBS for 1 h treated overnight with antibodies to eNOS (Transduction Transduction Laboratory USA and NADPH Oxidase (p47 p47 phox |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | to eNOS (Transduction Transduction Laboratory USA and NADPH Oxidase (p47 p47 phox pg91 phox Santa Cruz Biotechnology Inc. Santa Cruz CA |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | Diabetes-associated alterations in the eNOS enzyme system |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | As NO in vascular endothelial cells is synthesized primarily by eNOS we examined the possibility that a diabetes-related decrease in NO |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | Unexpectedly our data revealed that the expression of eNOS was elevated as a function of diabetes ( Fig 2 |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | Thus there appears to be a sharp dissociation between eNOS and its product NO in the vascular tissue of GK |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | in the present study to confirm that the overexpression of eNOS was associated with a similar increase in its activity in |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | segments or treating them with l -NAME an inhibitor of NOS activity |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | aortic tissue of GK rats together with the overexpression of eNOS raised a possibility that the NOS system is dysregulated during |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | with the overexpression of eNOS raised a possibility that the NOS system is dysregulated during diabetes |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | In its absence purified eNOS produces reactive oxygen species rather than NO ( Vasquez-vivar et |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | Wever et al. 1997 a phenomenon which is known as eNOS uncoupling |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | view of these findings we tested the preposition that diabetes-induced eNOS uncoupling may stem from an abnormality in vascular tissue metabolism |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | of the membrane-bound (pg91 pg91 phox and the cytosolic (p47 p47 phox subunits of the NADPH oxidase system |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | data showed that the protein expression of pg91 phox and p47 phox in aortic tissues of GK rats was elevated over |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | SOD activity |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SODs | 0.9 | and the rate of removal by endogenous antioxidants (primarily primarily SODs |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | Within blood vessels the predominant isoform of SOD (when when expressed as percent of total SOD activity is |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | isoform of SOD (when when expressed as percent of total SOD activity is CuZnSOD ( Fukai et al. 1998 and Stralin |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | The activity of total SOD was also reduced in GK diabetic rats (GK, GK 6.97_amp_#xb1 |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | Accordingly we sought to investigate whether the increase in eNOS expression together with enhanced O 2 _amp_#x2212 production in aortic |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | phosphatidylinositol (PI) PI 3 kinase and protein kinase B(Akt), B Akt in the insulin signaling pathway were also reduced in this |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | including changes in the NO bioavailability or the expression of eNOS increased breakdown of NO due to augmented production of O |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | to a defect in NO-producing enzymes since the level of eNOS was upregulated in GK vascular tissues compared with their corresponding |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | A similar finding of increased eNOS expression has recently been reported in streptozotocin diabetic rats ( |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | high fructose diet displayed a decrease in aortic activity of eNOS ( Shinozaki et al. 2000 |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | Understanding this apparent paradox of diabetes-induced super induction of eNOS concomitantly with a decrease in vascular NO bioavailability dictated the |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | of these data it is reasonable to speculate that the eNOS enzyme system is overactivated in diabetic vessels as a compensatory |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | Alternatively or in a similar view an upregulation of eNOS can also occur in response to a number of physiological |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | anion levels thus substantiating our conclusion of the involvement of NOS in the overproduction of O 2 _amp_#x2212 during diabetes |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | This phenomenon of the so-called NOS uncoupling occurring in the GK rats may reflect a deficiency |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | diabetes may favor NAD(P)H NAD P H oxidase activity of NOS with subsequent formation of reactive oxygen species (O O 2 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | The exact mechanism whereby NOS generates O 2 _amp_#x2212 is uncertain |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | H pathways although it has other actions including inhibition of NOS ( Wang et al. 1993 |
| 2961 | DYNC1H1 | dynein, cytoplasmic 1, heavy chain 1 | P22 | 0.0 | subunits with those they make-up the membrane-bound cytochrome b 558 P22 phox and gp91 phox being important for electron transport or |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | technique revealed that the protein abundance of pg91 phox and p47 phox subunits of NAD(P)H NAD P H oxidase were elevated |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | apocynin in connection with the overexpression of gp91 phox and p47 phox in aortic tissue of GK rats harmonize with the |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | the diabetic state is hyperactive and this enzyme system like NOS may contribute at least in part for the overproduction of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | times faster than the scavenging of O 2 _amp_#x2212 by SOD implying that peroxynitrite formation can occur in vivo ( Beckman |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SODs | 0.9 | In addition to chemical antioxidants the defense include SODs which are present in mitochondria such as manganese SOD (MnSOD), |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | include SODs which are present in mitochondria such as manganese SOD (MnSOD), MnSOD cytosol such as CuZnSOD and plasma membrane and |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | which are present in mitochondria such as manganese SOD (MnSOD), MnSOD cytosol such as CuZnSOD and plasma membrane and extracellular spaces |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | CuZnSOD and plasma membrane and extracellular spaces such as extracellular SOD catalase glutathione peroxidase and thioredoxin ( Sawyer et al. 2002 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | data indicate that cytosolic CuZnSOD activity (predominant predominant isoform of SOD in vessels was reduced whereas isoprostane and protein-bound carbonyl levels |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | NADH/NAD(P)H NADH NAD P H oxidase and the uncoupling of eNOS would provide a reasonable explanation for the diminished response to |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | Fig 2._amp_#xa0 Aortic NO bioavailability and eNOS expression during diabetes |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 3.2 | (B) B Representative Western blot analysis of eNOS protein expression in aortas of Wistar and GK rats 50 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | (A) A Representative Western blot analysis of p47 phox pg91 phox protein expression in aortas of Wistar and |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | SDS-PAGE transferred to nitrocellulose membrane and probed with antibody against p47 phox pg91 phox as described in Materials and methods |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | iquid chromatography hplc based techniques revealed respectively that the above inverse relationship between o 2 _amp_#x2212; and no was associated with a marked increase in the protein expression of nitric oxide synthase enos and a decrease in the level of its cofactor tetrahydrobiopterin bh 4 in diabetic aortas. |
| 6081 | INS | insulin | insulin | 1.0 | insulin resistance and endothelial dysfunction appear to exist in a variety of metabolic and cardiovascular disorders including atherosclerosis and type ii diabetes pinkney et al. 1997 . |
| 6081 | INS | insulin | insulin | 1.0 | drugs that enhance insulin sensitivity e.g troglitazone vitamin c lower blood pressure in both human and animal studies paolisso et al. 1994 and ogihara et al. 1995 . |
| 6081 | INS | insulin | insulin | 1.0 | likewise agents that lower peripheral vascular resistance in hypertensive subjects e.g angiotensin converting enzyme inhibitors also improve insulin sensitivity torlone et al. 1991 . |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | angiotensin converting enzyme | 1.0 | likewise agents that lower peripheral vascular resistance in hypertensive subjects e.g angiotensin converting enzyme inhibitors also improve insulin sensitivity torlone et al. 1991 . |
| 6081 | INS | insulin | insulin | 1.0 | because insulin sensitivity is susceptible to changes in whole body redox balance oxidative stress may be involved in the development of insulin resistance. |
| 6081 | INS | insulin | insulin | 1.0 | indeed insulin resistant obese zucker rats rapidly develop a type ii diabetes like state when exposed to a pro oxidative insult laight et al. 1999 . |
| 6081 | INS | insulin | insulin | 1.0 | in view of the above information a hypothesis was formulated stating that endothelial dysfunction and insulin resistance are associated with a heightened state of oxidative stress in diabetes mellitus. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | o 2 _amp_#x2212; concentration in aortic tissue was determined using a lucigenin enhanced chemiluminescence method li y zhu et al. 1998 and the resulting data were further confirmed by a cytochrome c based technique liochev and fridovich 1997 and kuthan and ulrich 1982 . |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | the amount of o 2 _amp_#x2212; produced was quantified using a standard curve of o 2 _amp_#x2212; generation by xanthine/xanthine oxidase and the data are expressed as nmol per min per mg of wet weight. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | superoxide production was also determined using the superoxide dismutase sod inhibitable cytochrome c assay. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | superoxide production was also determined using the superoxide dismutase sod inhibitable cytochrome c assay. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | cytochrome c 50 _amp_#x3bc;m was added and the reaction mixture was incubated at 37 _amp_#xb0;c for 60 min with or without sod 200 u/ml . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | cytochrome c reduction was measured by reading absorbance at 550 nm. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | the sod dependent inhibition of cytochrome c reduction catalyzed by xanthine oxidase was assessed spectrophotometrically by monitoring the absorbance at 550 nm for 2 min at 37 _amp_#xb0;c okado matsumoto and fridovich 2001 . |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | the sod dependent inhibition of cytochrome c reduction catalyzed by xanthine oxidase was assessed spectrophotometrically by monitoring the absorbance at 550 nm for 2 min at 37 _amp_#xb0;c okado matsumoto and fridovich 2001 . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | briefly the reaction mixture contained 0.1 mm edta 0.09 mm xanthine 0.018 mm cytochrome c 50 mm potassium buffer ph 7.8 and the cellular extract supernatant. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | the assay was calibrated by adding xanthine oxidase at a concentration that increased the absorbance of the mixture by 0.025 per min as a result of cytochrome c reduction. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | the assay was calibrated by adding xanthine oxidase at a concentration that increased the absorbance of the mixture by 0.025 per min as a result of cytochrome c reduction. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | one sod unit is arbitrary defined as the amount of enzyme required to inhibit the reduction rate of cytochrome c by 50%. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | enzymatic activity in arbitrary units per milligram of total proteins was determined by calculating from the slope of the absorbance curves the percentage inhibition of cytochrome c reduction in the test samples relative to the controls. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | western blot analysis for enos and protein subunits of nadph oxidase |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | blots were blocked in 5% skimmed nonfat milk in pbs for 1 h treated overnight with antibodies to enos transduction laboratory usa and nadph oxidase p47 phox pg91 phox santa cruz biotechnology inc. santa cruz ca usa and then incubated with peroxidase conjugated secondary antibodies for 1 h. |
| 6081 | INS | insulin | insulin | 1.0 | assessment of in vivo insulin action |
| 6081 | INS | insulin | insulin | 1.0 | insulin sensitivity was determined by the steady state plasma glucose sspg method with the use of somatostatin harano et al. 1981 . |
| 11329 | SST | somatostatin | somatostatin | 1.0 | insulin sensitivity was determined by the steady state plasma glucose sspg method with the use of somatostatin harano et al. 1981 . |
| 6081 | INS | insulin | insulin | 1.0 | an infusate containing somatostatin 120 _amp_#x3bc;g/kg/h glucose 1.0 g/kg/h and insulin 2.0 u/kg/h human actrapid novo nordisk was administered intravenously to control and gk rats at a flow rate of 2.8 ml/h for 120 min. |
| 11329 | SST | somatostatin | somatostatin | 1.0 | an infusate containing somatostatin 120 _amp_#x3bc;g/kg/h glucose 1.0 g/kg/h and insulin 2.0 u/kg/h human actrapid novo nordisk was administered intravenously to control and gk rats at a flow rate of 2.8 ml/h for 120 min. |
| 6081 | INS | insulin | insulin | 1.0 | the sspg levels and the steady state plasma insulin sspi contents were determined at 120 min following the start of the infusion. |
| 6081 | INS | insulin | insulin | 1.0 | plasma glucose and free fatty acid concentrations were measured according to the standard enzymatic assays while insulin level was determined using a radioimmunoassay with anti rat insulin antibody. 2.9. |
| 399 | ALB | albumin | serum albumin | 1.0 | tissue protein content was determined as described previously lowry et al. 1951 using bovine serum albumin as a standard. 2.10. |
| 6081 | INS | insulin | insulin | 1.0 | similarly plasma concentrations of insulin and free fatty acids were also increased in these animals. |
| 6081 | INS | insulin | insulin | 1.0 | insulin sensitivity as indicated by the sspg level was diminished as a function of diabetes table 1 . |
| 6081 | INS | insulin | insulin | 1.0 | these data are consistent with the concept that this genetic animal model of type ii diabetes exhibits alterations in lipid and carbohydrate profiles with an evidence of insulin resistance. 3.2. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | to confirm the validity of the lucigenin technique for measurement of o 2 _amp_#x2212; in our animal mode of diabetes we also assessed vascular basal o 2 _amp_#x2212; formation by the cytochrome c method. |
| 6081 | INS | insulin | insulin | 1.0 | o 2 _amp_#x2212; production by aortic rings from the diabetic insulin resistant animals 2.87_amp_#xb1;0.18 nmol/min/mg tissue was significantly higher than that of corresponding control values 1.61_amp_#xb1;0.23 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase constitutes a major source of reactive oxygen species production in both the intact vessels and cultured vascular smooth muscle cells patrono and fitzgerald 1997 and pagano et al. 1995 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the resulting data showed that both diphenyleneiodonium and apocynin inhibitors of nadph oxidase significantly reduced o 2 _amp_#x2212; formation in gk diabetic rats table 3 . 3.5. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | diphenyleneiodonium inhibits several reactive oxygen species generating flavin containing enzymes besides nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | accordingly we conducted an additional experiment involving the immunoblotting of measurement of the levels of expression of the membrane bound pg91 phox and the cytosolic p47 phox subunits of the nadph oxidase system. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | together the immunoblotting data in connection with the inhibitor studies e.g diphenyleneiodonium apocynin of the nadph oxidase support the involvement of this enzyme system in the overproduction of vascular o 2 _amp_#x2212; during diabetes. 3.7. |
| 6081 | INS | insulin | insulin | 1.0 | the central hypothesis of our research is consistent with the concept that a heightened state of oxidative stress is involved in the development of insulin resistance and this phenomenon constitutes an integral part of several cardiovascular risk factors including essential hypertension dyslipidemia obesity glucose intolerance and diabetes mellitus reav |
| 6081 | INS | insulin | insulin | 1.0 | in this connection a number of insulin resistance states appear to be associated with insulin's impaired ability to increase blood flow together with vasospastic angina and obstructive coronary artery disease shinozaki et al. 1995 and shinozaki et al. 1996 . |
| 6081 | INS | insulin | insulin | 1.0 | the current data revealed that the in vivo insulin action assessed by the steady state plasma glucose method was reduced in gk rats when compared to corresponding wistar control values. |
| 6081 | INS | insulin | insulin | 1.0 | similarly skeletal muscle activities of two key enzymes e.g. phosphatidylinositol pi 3 kinase and protein kinase b akt in the insulin signaling pathway were also reduced in this genetic animal model of non obese type ii diabetes bitar et al. 2004 . |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | protein kinase b | 1.0 | similarly skeletal muscle activities of two key enzymes e.g. phosphatidylinositol pi 3 kinase and protein kinase b akt in the insulin signaling pathway were also reduced in this genetic animal model of non obese type ii diabetes bitar et al. 2004 . |
| 6081 | INS | insulin | insulin | 1.0 | this insulin resistance state was associated with an impaired arterial response to acetylcholine and sodium nitroprusside indicating that gk rats exhibit a dysfunctional endothelium and decreased smooth muscle se |
| 6081 | INS | insulin | insulin | 1.0 | it is worthy of note that sprague_amp_#x2013;dawley rats rendered insulin resistant by a high fructose diet displayed a decrease in aortic activity of enos shinozaki et al. 2000 . |
| 3676 | FGF2 | fibroblast growth factor 2 (basic) | basic fibroblast growth factor | 1.0 | f physiological stimuli including shear stress ranjan et al. 1995 cytokines and growth promoting polypeptides inoue et al. 1995 and kostyk et al. 1995 as in the case of transforming growth factor and basic fibroblast growth factor. |
| 11765 | TGFA | transforming growth factor, alpha | transforming growth factor | 1.0 | occur in response to a number of physiological stimuli including shear stress ranjan et al. 1995 cytokines and growth promoting polypeptides inoue et al. 1995 and kostyk et al. 1995 as in the case of transforming growth factor and basic fibroblast growth factor. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | nadh/nad p h oxidase xanthine oxidase a dysfunctional no synthetase or mitochondrial flavoproteins represent an important source for reactive oxygen species generation within vascular endothelial and smooth muscle cells wever et al. 1998 |
| 2595 | CYP1A1 | cytochrome P450, family 1, subfamily A, polypeptide 1 | cytochrome p 450 | 1.0 | however molecular cloning of no synthetase revealed close amino acid sequence homology between no synthetase and cytochrome p 450 reductase a known cellular source of superoxide anion bredt et al. 1991 . |
| 9208 | POR | P450 (cytochrome) oxidoreductase | cytochrome p 450 reductase | 1.0 | however molecular cloning of no synthetase revealed close amino acid sequence homology between no synthetase and cytochrome p 450 reductase a known cellular source of superoxide anion bredt et al. 1991 . |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | the vascular nad p h oxidase consists of at least 3_amp_#x2013;5 subunits with those they make up the membrane bound cytochrome b 558 p22 phox and gp91 phox being important for electron transport or the reduction of molecular oxygen to o 2 _amp_#x2212; . |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | the vascular nad p h oxidase consists of at least 3_amp_#x2013;5 subunits with those they make up the membrane bound cytochrome b 558 p22 phox and gp91 phox being important for electron transport or the reduction of molecular oxygen to o 2 _amp_#x2212; . |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | the vascular nad p h oxidase consists of at least 3_amp_#x2013;5 subunits with those they make up the membrane bound cytochrome b 558 p22 phox and gp91 phox being important for electron transport or the reduction of molecular oxygen to o 2 _amp_#x2212; . |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | taken together the inhibition of o 2 _amp_#x2212; production by diphenyleneiodonium and apocynin in connection with the overexpression of gp91 phox and p47 phox in aortic tissue of gk rats harmonize with the notion that the nad p h oxidase in the diabetic state is hyperactive and this enzyme system like nos may contribute at least in part for th |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | similarly angiotensin ii is also a potent stimulus of the nad p h oxidase griendling et al. 1994 . |
| 336 | AGTR1 | angiotensin II receptor, type 1 | angiotensin ii receptor | 1.0 | the gk rats are hypertensive and the vascular expression of angiotensin ii receptor is upregulated as a function of diabetes candido et al. 2004 . |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | mn superoxide dismutase | 1.0 | similarly nitration of prostacyclin synthetase and mn superoxide dismutase induced by overproduction of peroxynitrite have been shown to contribute to the development of endothelial dysfunction in a number of disease states including atherosclerosis and aging beckman et al. |
| 12435 | TXN | thioredoxin | thioredoxin | 1.0 | e sods which are present in mitochondria such as manganese sod mnsod cytosol such as cuznsod and plasma membrane and extracellular spaces such as extracellular sod catalase glutathione peroxidase and thioredoxin sawyer et al. 2002 and sorescu and griendling 2002 . |
| 1516 | CAT | catalase | catalase | 1.0 | ical antioxidants the defense include sods which are present in mitochondria such as manganese sod mnsod cytosol such as cuznsod and plasma membrane and extracellular spaces such as extracellular sod catalase glutathione peroxidase and thioredoxin sawyer et al. 2002 and sorescu and griendling 2002 . |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | of course our results do not exclude a role for other potential sources of o 2 _amp_#x2212; e.g xanthine oxidase mitochondrial flavoproteins within diabetic vascular cells. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | fig. 4._amp_#xa0;expression of protein subunits of nadph oxidase in aortic tissue of diabetics. |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | nes|protein subunits|proteins|vasodilator agents|nitric oxide|superoxides|nitroprusside|5 6 7 8 tetrahydrobiopterin|biopterin|3 nitrotyrosine|ng nitroarginine methyl ester|tyrosine|nos3 protein human|nitric oxide synthase|nitric oxide synthase type iii|nos3 protein rat|superoxide dismutase|nadph oxidase| |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | |nitric oxide synthase type iii|nos3 protein rat|superoxide dismutase|nadph oxidase| |