Effect of telmisartan on expression of protein kinase C-alpha in kidneys of diabetic mice.
OBJECTIVE
To investigate the effects of angiotensin receptor blocker (ARB) telmisartan on the expression and distribution of protein kinase C (PKC)-alpha in the kidneys of diabetic mice.


METHODS
Diabetic mice were induced with streptozotocin and a group of them were randomly selected for treatment with telmisartan. After 6 weeks, the expression and localization of PKC-alpha in the renal cortex, and the outer and inner medulla were assessed by immunohistochemistry and semiquantitative Western blotting. In addition, expressions of PKC-alpha, transforming growth factor-beta1 (TGF-beta1), and vascular endothelial growth factor (VEGF) in glomeruli were measured by semiquantitative immunohistochemistry.


RESULTS
Diabetic and normal mice showed similar distributions of PKC-alpha in the kidneys. The expression of PKC-alpha was found in glomeruli, epithelial cells of proximal tubules, and medullary-collecting duct, while not in the medullary and cortical thick ascending limb, and was different in the epithelial cells of proximal tubules of diabetic nephropathy (DN) mice, PKC-alpha was mostly translocated from the basement membrane to the apical membrane, whereas it was largely translocated from the apical membrane to the basement membrane in epithelial cells of the inner medullary-collecting duct. Western blotting detected increased expression of PKC-alpha in the renal cortex and outer medulla, but not in the inner medulla of DN mice. Enhanced expressions of PKC-alpha, TGF-beta1, and VEGF were shown in the glomeruli of DN mice, where PKC-alpha exhibited a correlation to VEGF, but no correlation to TGF-beta1. ARB telmisartan attenuated alterations of PKC-alpha as mentioned earlier in the DN mice.


CONCLUSIONS
Our findings suggest that PKC-alpha may play a role in the pathogenesis of DN, and that the nephroprotective effects of ARB telmisartan may be partly associated with its influence on PKC-alpha.
Yao
Li-Jun
LJ
Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. yaolijun1971@yahoo.com
Wang
Jian-Qing
JQ
Zhao
Hong
H
Liu
Jian-She
JS
Deng
An-Guo
AG
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D000077333:Telmisartan; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D051571:Protein Kinase C-alpha; D000077333:Telmisartan