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10.1161/HYPERTENSIONAHA.109.145714

http://scihub22266oqcxt.onion/10.1161/HYPERTENSIONAHA.109.145714
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C4586163!4586163!20038746
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suck abstract from ncbi


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pmid20038746      Hypertension 2010 ; 55 (2): 468-73
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  • Protein Kinase C-Dependent NAD(P)H Oxidase Activation Induced by Type 1 Diabetes in Renal Medullary Thick Ascending Limb #MMPMID20038746
  • Yang J; Lane PH; Pollock JS; Carmines PK
  • Hypertension 2010[Feb]; 55 (2): 468-73 PMID20038746show ga
  • Type 1 diabetes provokes a protein kinase C (PKC)-dependent accumulation of superoxide anion in the renal medullary thick ascending limb (mTAL). We hypothesized that this phenomenon involves PKC-dependent NAD(P)H oxidase activation. The validity of this hypothesis was explored using mTAL suspensions prepared from rats with streptozotocin-induced diabetes and from sham (vehicle-treated) rats. Superoxide production was 5-fold higher in mTAL suspensions from diabetic rats compared with suspensions from sham rats. The NAD(P)H oxidase inhibitor apocynin caused an 80% decrease in superoxide production by mTALs from diabetic rats (P<0.05 vs untreated) without altering superoxide production by sham mTALs. NAD(P)H oxidase activity was more than two-fold higher in mTALs from diabetic rats than in sham mTALs (P<0.05). Pretreatment with calphostin C (broad-spectrum PKC inhibitor) or rottlerin (PKC? inhibitor) reduced NAD(P)H oxidase activity by ~80% in both groups; however, PKC?/? or PKC? inhibition did not alter NAD(P)H oxidase activity in either group. Protein levels of Nox2, Nox4 and p47phox were significantly higher in diabetic mTALs than in mTALs from sham rats. In summary, elevated superoxide production by mTALs from diabetic rats was normalized by NAD(P)H oxidase inhibition. PKC-dependent, PKC?-dependent, and total NAD(P)H oxidase activity was greater in mTALs from diabetic rats compared with sham. Protein levels of Nox2, Nox4 and p47phox were increased in mTALs from diabetic rats. We conclude that increased superoxide production by the mTAL during diabetes involves a PKC?-dependent increase in NAD(P)H oxidase activity, in concert with increased protein levels of catalytic and regulatory subunits of the enzyme.
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