Effects of Blocking the Renin-Angiotensin System on Expression and Translocation of Protein Kinase C Isoforms in the Kidney of Diabetic Rats

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 alpha and betaII 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-alpha and -betaII in the renal cortex and medulla were assessed by immunohistochemistry and Western immunoblotting. RESULTS: The expression of PKC-alpha 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-betaII 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-alpha and -betaII 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.