Document Information


PMID 12639760  (  )
Title Enhanced vascular production of superoxide in OLETF rat after the onset of hyperglycemia.
Abstract This study was aimed to characterize the vascular production of superoxide in Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type 2 diabetes. The nitroblue tetrazolium staining in the aorta from old (30 weeks) OLETF rat was more prominent than that of age-matched control (LETO) rat, which was significantly inhibited by diphenyleneiodonium (10 micromol/l), but not by inhibitors for other oxidases such as xanthine oxidase, mitochondrial oxidase, nitric oxide synthase, and cyclooxygenase. In the aorta from old OLETF rat with hyperglycemia, the enhanced NADH oxidase activity in association with upregulated expression of p22phox and gp91phox was observed, but not in both LETO and young (10 weeks) OLETF rats without hyperglycemia. Furthermore, there was a positive correlation (P<0.01) between elevation of blood glucose level and increase in vascular NADH oxidase activity. Based on these results, it was suggested that the enhanced NADH oxidase activity in the aorta from OLETF rat occurred after the onset of hyperglycemia, thereby resulting in the increased vascular production of superoxide. Pusan National University, Busan 602-739, South Korea.

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Targets by SciMiner Summary

HUGO ID Symbol Target Name #Occur ActualStr
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)13gp91phox |
2577CYBAcytochrome b-245, alpha polypeptide13p22phox |
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))7SOD |
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)3nitric oxide synthase |
12805XDHxanthine dehydrogenase3xanthine oxidase |
14874NOX5NADPH oxidase, EF-hand calcium binding domain 52nadph oxidase |
7661NCF2neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)1p67phox |
391AKT1v-akt murine thymoma viral oncogene homolog 11rac |
9393PRKCAprotein kinase C, alpha1protein kinase c |
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)1angiotensin ii |
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)1p47phox |

 


Targets by SciMiner Full list

HUGO ID Symbol Name ActualStr Score FlankingText
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.8enhanced NADH oxidase activity in association with upregulated expression of p22phox and gp91phox was observed but not in both LETO and
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox2.3oxidase activity in association with upregulated expression of p22phox and gp91phox was observed but not in both LETO and young (10
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD0.3incubated for 30 min in the presence or absence of SOD (200 200 U/ml), U ml tiron (10 10 mM diphenyleneiodonium
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.8Western blot for p22phox and gp91phox
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox2.3Western blot for p22phox and gp91phox
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.8milk the transferred membrane was then incubated with antibodies against p22phox and gp91phox (goat goat polyclonal antibody Santa Cruz Biotech
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox2.3transferred membrane was then incubated with antibodies against p22phox and gp91phox (goat goat polyclonal antibody Santa Cruz Biotech
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD0.3The superoxide scavengers SOD (200 200 U/ml) U ml and tiron (10 10 mmol/l),
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD0.3The effect of tiron was greater than that of SOD 3.3
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.8Expression of p22phox and gp91phox
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox2.3Expression of p22phox and gp91phox
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.8We examined protein expression for p22phox and gp91phox in the aorta from old OLETF rat by
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox2.3We examined protein expression for p22phox and gp91phox in the aorta from old OLETF rat by Western blot
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.8As shown in Fig 5 p22phox and gp91phox protein expression in the vasculature from OLETF rat
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox2.3As shown in Fig 5 p22phox and gp91phox protein expression in the vasculature from OLETF rat was significantly
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.8enhanced activity of vascular NADH oxidase with upregulated expression of p22phox and gp91phox was evident in the aorta from old OLETF
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox2.3of vascular NADH oxidase with upregulated expression of p22phox and gp91phox was evident in the aorta from old OLETF rat (4)
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD0.3assay was further indicated by showing that the superoxide scavengers SOD and tiron decreased the reduction of NBT
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD0.3In our experiment SOD decreased NBT reduction to a lesser extent than did tiron
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD0.3In contrast at least in the short term exogenous SOD only has access to superoxide generated extracellularly since it is
7660NCF1neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)p47phox1.0H oxidase complex is composed of several cytoplasmic factors (p47phox, p47phox p67phox and rac and a membrane-bound flavocytochrome b558 consisting of
7661NCF2neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)p67phox1.0oxidase complex is composed of several cytoplasmic factors (p47phox, p47phox p67phox and rac and a membrane-bound flavocytochrome b558 consisting of a
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.8membrane-bound flavocytochrome b558 consisting of a small _amp_#x3b1 -subunit (p22phox) p22phox and a larger glycosylated _amp_#x3b2 -subunit gp91phox 19 20 21
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox2.3_amp_#x3b1 -subunit (p22phox) p22phox and a larger glycosylated _amp_#x3b2 -subunit gp91phox 19 20 21 22 and 23
391AKT1v-akt murine thymoma viral oncogene homolog 1rac0.1is composed of several cytoplasmic factors (p47phox, p47phox p67phox and rac and a membrane-bound flavocytochrome b558 consisting of a small _amp_#x3b1
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox2.3membrane-bound subunits of NAD(P)H NAD P H oxidase such as gp91phox and p22phox are essential for the stability of oxidase and
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.8of NAD(P)H NAD P H oxidase such as gp91phox and p22phox are essential for the stability of oxidase and its catalytic
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox2.3activation in OLETF rat we determined the protein expression of gp91phox and p22phox by Western blot analysis
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.8OLETF rat we determined the protein expression of gp91phox and p22phox by Western blot analysis
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.8Our results clearly showed that the expression of both p22phox and gp91phox in the aorta from OLETF rat was significantly
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox2.3results clearly showed that the expression of both p22phox and gp91phox in the aorta from OLETF rat was significantly higher than
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.8In summary upregulated expression of p22phox and gp91phox enhanced NADH oxidase activity subsequently causing the accelerated
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox2.3In summary upregulated expression of p22phox and gp91phox enhanced NADH oxidase activity subsequently causing the accelerated adventitial production
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD0.3several inhibitors such as tiron (10 10 mmol/l), mmol l SOD (200 200 U/ml), U ml DPI (10 10 _amp_#x3bc;mol/l), _amp_#x3bc
2577CYBAcytochrome b-245, alpha polypeptidep22phox0.8Representative Western blots analysis for p22phox gp91phox and _amp_#x3b2 -actin in the aortas from LETO and
2578CYBBcytochrome b-245, beta polypeptide (chronic granulomatous disease)gp91phox2.3Representative Western blots analysis for p22phox gp91phox and _amp_#x3b2 -actin in the aortas from LETO and OLETF
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)nitric oxide synthase1.0at of age matched control leto rat which was significantly inhibited by diphenyleneiodonium 10 _amp_#x3bc;mol/l but not by inhibitors for other oxidases such as xanthine oxidase mitochondrial oxidase nitric oxide synthase and cyclooxygenase.
12805XDHxanthine dehydrogenasexanthine oxidase1.0ks oletf rat was more prominent than that of age matched control leto rat which was significantly inhibited by diphenyleneiodonium 10 _amp_#x3bc;mol/l but not by inhibitors for other oxidases such as xanthine oxidase mitochondrial oxidase nitric oxide synthase and cyclooxygenase.
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)nitric oxide synthase1.0dpi 10 _amp_#x3bc;mol/l but not by other inhibitors such as allopurinol xanthine oxidase inhibitor 300 _amp_#x3bc;mol/l rotenone inhibitor of mitochondrial electron transport 50 _amp_#x3bc;mol/l nmma nitric oxide synthase inhibitor 300 _amp_#x3bc;mol/l and indomethacin cyclooxygenase inhibitor 100 _amp_#x3bc;mol/l .
12805XDHxanthine dehydrogenasexanthine oxidase1.0the increased nbt reduction in the aorta from oletf rat was greatly reduced by treatment with an nad p h oxidase inhibitor dpi 10 _amp_#x3bc;mol/l but not by other inhibitors such as allopurinol xanthine oxidase inhibitor 300 _amp_#x3bc;mol/l rotenone inhibitor of mitochondrial electron transport 50 _amp_#x3bc;mol/l nmma nitric oxide synthase inhibitor 300 _amp_#x3bc;mol/l and indomethacin cyclooxygenase inh
14874NOX5NADPH oxidase, EF-hand calcium binding domain 5nadph oxidase1.0recently in angiotensin ii induced hypertension wang et al. [ 16 ] demonstrated that the production of superoxide and the expression of nadph oxidase subunits remain primarily localized in the adventitia and adventitial superoxide played a paracrine role in mediating spontaneous tone of the aorta.
333AGTangiotensinogen (serpin peptidase inhibitor, clade A, member 8)angiotensin ii1.0recently in angiotensin ii induced hypertension wang et al. [ 16 ] demonstrated that the production of superoxide and the expression of nadph oxidase subunits remain primarily localized in the adventitia and adventitial supero
7873NOS2Anitric oxide synthase 2A (inducible, hepatocytes)nitric oxide synthase1.0ction in the aorta from oletf rat was significantly reduced by treatment with dpi an nad p h oxidase inhibitor but not by inhibitors for other oxidases such as xanthine oxidase mitochondrial oxidases nitric oxide synthase and cyclooxygenase suggesting that nad p h oxidase is involved in the vascular production of superoxide in oletf rat.
12805XDHxanthine dehydrogenasexanthine oxidase1.0the enhanced nbt reduction in the aorta from oletf rat was significantly reduced by treatment with dpi an nad p h oxidase inhibitor but not by inhibitors for other oxidases such as xanthine oxidase mitochondrial oxidases nitric oxide synthase and cyclooxygenase suggesting that nad p h oxidase is involved in the vascular production of superoxide in oletf rat.
9393PRKCAprotein kinase C, alphaprotein kinase c1.0based on these results with others that high glucose stimulates the production of ros through protein kinase c dependent activation of nad p h oxidase in vascular smooth muscle cells [ 26 ] it is likely that the enhanced activity of vascular nadh oxidase in old oletf rat is closely related with hyperglycemia
14874NOX5NADPH oxidase, EF-hand calcium binding domain 5nadph oxidase1.0cybb protein human|membrane glycoproteins|membrane transport proteins|multienzyme complexes|phosphoproteins|superoxides|nadh oxidase|nadh nadph oxidoreductases|cyba protein human|nadph oxidase|nadph dehydrogenase|