Effect of telmisartan on expression of protein kinase C-? in kidneys of diabetic mice

Abstract

Aim: To investigate the effects of angiotensin receptor blocker (ARB) telmisartan on the expression and distribution of protein kinase C (PKC)-α 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-α in the renal cortex, and the outer and inner medulla were assessed by immunohistochemistry and semiquantitative Western blotting. In addition, expressions of PKC-α, transforming growth factor-β1 (TGF-β1), and vascular endothelial growth factor (VEGF) in glomeruli were measured by semiquantitative immunohistochemistry. Results: Diabetic and normal mice showed similar distributions of PKC-α in the kidneys. The expression of PKC-α was found in glomeruli, epithelial cells of proximal tubules, and medullarycollecting 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-α 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-α in the renal cortex and outer medulla, but not in the inner medulla of DN mice. Enhanced expressions of PKC-α, TGF-β1, and VEGF were shown in the glomeruli of DN mice, where PKC-α exhibited a correlation to VEGF, but no correlation to TGF-β1. ARB telmisartan attenuated alterations of PKC-α as mentioned earlier in the DN mice. Conclusion: Our findings suggest that PKC-α 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-α.

Inhibitory Effects of the Constituents of <i>Hippophae rhamnoides</i> on 3T3-L1 Cell Differentiation and Nitric Oxide Production in RAW264.7 Cells

“…Eight compounds were isolated from the chloroform layer. Compounds 4-30 were identified by detailed comparisons of their spectroscopic data with those in the literature as kaempferol (4), 13) 16) tiliroside (8), 3) quercetin (9), 17) rutin (10), 18) 24) isorhamnetin 3-O-β-d-glucopyranoside (17), 15) gallic acid (18), 25) methyl gallate (19), 26) 4-hydroxybenzoic acid (20), 27) protocatechuic acid (21), 28) methyl brevifolincarboxylate (22), 29) ursolic acid (23), 30) ursolic aldehyde (24), 31) 28-nor-urs-12-ene-3β,17β-diol (25), 32) pomolic acid (26), 33) 2α-hydroxy ursolic acid (27), 33) 23-hydroxy ursolic acid (28), 34) vomifoliol (29), 35) and β-sitosterol (30) 30) (Fig. 1).…”

Protein kinase C-α mediates hypertonicity-stimulated increase in urea transporter phosphorylation in the inner medullary collecting duct

“…Next, we asked whether the increase in UT-A1 phosphorylation was specific to hypertonicity or could be mimicked by directly activating PKC using a phorbol ester. Finally, we tested whether PKC-␣, a calcium-dependent PKC isoform that is expressed in the IMCD (16,22), is specifically involved in the response to hypertonicity.…”

Renoprotective Effects of Various Angiotensin II Receptor Blockers in Patients with Early-Stage Diabetic Nephropathy

“…Thus, we have new insight into the beneficial mechanisms of antihypertensive agents in the treatment of renal diseases induced by oxidative stress such as diabetic nephropathy. In animal models, telmisartan has a definite renoprotective effect against renal injury in type 2 diabetic nephropathy [35,36] . In the present study, telmisartan was shown to be more effective than losartan, candesartan and olmesartan in reducing UAE, urinary 8-OHdG, and urinary L-FABP levels in early-stage diabetic nephropathy patients.…”