High glucose and diabetes enhanced store-operated ca2+ entry and increased expression of its siganling proteins in mesangial cells.

HIGH GLUCOSE AND DIABETES ENHANCED STORE-OPERATED CA2+ ENTRY AND INCREASED EXPRESSION OF ITS SIGANLING PROTEINS IN MESANGIAL CELLS. Am J Physiol Renal Physiol. 2014 Mar 12; Authors: Chaudhari S, Wu P, Wang Y, Ding Y, Yuan J, Begg M, Ma R Abstract The present study was conducted to determine whether and how store-operated Ca(2+) entry (SOCE) in glomerular mesangial cells (MCs) was altered by high glucose (HG) and diabetes. Human MCs were treated with either normal glucose or HG for different time periods. Cyclopiazonic acid-induced SOCE was significantly greater in the MCs with 7 day HG treatment and the response was completely abolished by GSK-7975A, a selective inhibitor of store-operated Ca(2+) channel. Similarly, the inositol 1,4,5-trisphosphate-induced store-operated Ca(2+) currents were significantly enhanced in the MCs treated with HG for 7 days and the enhanced response was abolished by both GSK-7975A and La3+. In contrast, receptor-operated Ca(2+) entry in MCs was significantly reduced by HG treatment. Western blot showed that HG increased the expression levels of STIM1 and Orai1 in cultured MCs. A significant HG effect occurred at a concentration as low as 10 mM, but required a minimum of 7 days. The HG effect in cultured MCs was recapitulated in renal glomeruli/cortex of both type I and II diabetic rats. Furthermore, quantitative real time RT-PCR revealed that a 6 day HG treatment significantly increased mRNA expression level of STIM...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research