Protein kinase C beta isoenzymes in diabetic kidneys and their relation to nephroprotective actions of the ACE inhibitor lisinopril.
Inhibitors of angiotensin-converting enzyme (ACE) or beta isoforms of protein kinase C (PKC) are nephroprotective in diabetes mellitus. We investigated the influence of streptozotocin (STZ)-induced diabetes mellitus and of treatment with the ACE inhibitor lisinopril (4 mg/kg p.o. twice daily for 4 weeks) on the expression of PKC beta 1 and PKC beta 2 in the renal cortex of female Sprague-Dawley rats. Immunohistochemistry indicated an enhanced renocortical accumulation of macrophages expressing both MHC II, a marker for antigen-presenting cells, as well as PKC beta 2 in STZ diabetes which was confirmed by Western blotting demonstrating an enhanced renocortical expression of MHC II (1.8-fold) as well as of membrane-associated PKC beta 2 (1.9-fold). Whereas immunohistochemistry could not detect unequivocal alterations, Western blotting showed a rise in the renocortical expression of membrane-associated PKC beta 1 (1.7-fold) in STZ diabetes. Lisinopril lowered renocortical albumin content and proteinuria in STZ diabetes and attenuated the enhanced accumulation of macrophages expressing PKC beta 2 as well as the increase of membrane-associated expression of PKC beta 1 and PKC beta 2 in the renal cortex. The data suggest that the nephroprotective actions of the ACE inhibitor lisinopril in experimental diabetes mellitus were associated with and thus could be mediated in part by inhibition of diabetes-induced activation of PKC beta isoenzymes in the renal cortex.
Pfaff
Imke L
IL
Department of Pharmacology, Faculty of Medicine, University of Tübingen, Germany.
Vallon
Volker
V
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D019610:Cytoprotection; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D005260:Female; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D017706:Lisinopril / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D017706:Lisinopril; D011493:Protein Kinase C; D064546:Protein Kinase C beta