High glucose-induced Nox1-derived superoxides downregulate PKC-βII, which subsequently decreases ACE2 expression and ANG(1-7) formation in rat VSMCs

摘要: In rat diabetic animal models, ANG(1-7) treatment prevents the development of cardiovascular complications. Angiotensin-converting enzyme (ACE)2 is a major ANG(1-7)-generating in vascular smooth muscle cells (VSMCs), and its expression decreased by prolonged exposure to high glucose (HG), which reflected lower levels. However, underlying mechanism downregulation unknown was subject this study. Rat aortic VSMCs were maintained normal (NG) or HG (∼4.1 ∼23.1 mmol/l, respectively) for up 72 h. Several PKC NADPH oxidase inhibitors short interfering (si)RNAs used determine HG-induced ACE2 downregulation. Cell lysates subjected Western blot analysis, real-time quantitative PCR, radioimmunodetection. At h exposure, mRNA, protein, levels (0.17 ± 0.01-, 0.47 0.03-, 0.16 0.01-fold, respectively), subunit Nox1 increased (1.70 0.2-fold). The decrease reversed antioxidants siRNA as well glycotoxin formation. PKC-βII dependent, protein reduced presence (0.32 0.03-fold); however, inhibitor CG-53353 prevented loss induction, suggesting nonspecific effect inhibitor. Our data suggest that glycotoxin-induced regulated conventional PKCs. dependent. Nox1-derived superoxides reduce expression, lowers mRNA consequently decreases