Background: High glucose and angiotensin II (Ang II) can activate protein kinase C (PKC) in diabetes mellitus. However, it is not clear which isoform of PKC is activated by glucose or Ang II. Our study focused on the effects of angiotensin blockade, using the angiotensin-converting enzyme inhibitor fosinopril, the Ang II receptor blocker irbesartan and their combination, on the expression and translocation of PKC isoforms α and βII in the renal cortex and medulla in diabetes. Methods: Hyperglycemia was induced with streptozotocin and diabetic rats were randomized to 4 groups: diabetic control, irbesartan group (40 mg/kg daily), fosinopril group (40 mg/kg daily) and combination group (irbesartan plus fosinopril, 20 mg/kg daily, respectively); age-matched normal rats served as normal control. After 4 weeks, expression and translocation of PKC-α and -βII in the renal cortex and medulla were assessed by immunohistochemistry and Western immunoblotting. Results: The expression of PKC-α in the membrane and cytosol fractions from the renal cortex was significantly higher in diabetic rats (276.83 ± 32.44% in membrane, 149.04 ± 23.42% in cytosol) than that in normal ones. The expression of PKC-βII in the renal cortex of diabetic rats decreased significantly in the membrane (50.00 ± 11.68%, p < 0.05) and remained unchanged in the cytosol (94.51 ± 11.69%, p > 0.05) compared with normal controls. Treatment with irbesartan, fosinopril and their combination partially corrected the abnormalities mentioned above. For the expression of PKC-α and -βII in the medulla, no difference was detected among the 5 groups. Conclusion: The renin-angiotensin system was implicated in the pathogenesis of diabetic nephropathy by regulating the activation of PKC isoforms.

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