Lovastatin attenuates effects of cyclosporine A on tight junctions and apoptosis in cultured cortical collecting duct principal cells.

Lovastatin attenuates effects of cyclosporine A on tight junctions and apoptosis in cultured cortical collecting duct principal cells. Am J Physiol Renal Physiol. 2013 May 29; Authors: Liu BC, Song X, Lu XY, Fang C, Wei SP, Alli AA, Eaton DC, Shen BZ, Li XQ, Ma HP Abstract We used mouse cortical collecting duct principal cells (mpkCCDc14 line) as a model to determine whether statins reduce the harmful effects of cyclosporine A (CsA) on the distal nephron. The data showed that treatment of the cells with CsA increased transepithelial resistance and that the effect of CsA was abolished by lovastatin. Scanning ion conductance microscopy (SICM) showed that CsA significantly increased the height of cellular protrusions near tight junctions. In contrast, lovastatin eliminated the protrusions and even caused a modest depression between the cells. Western blots and confocal microscopy showed that lovastatin also abolished CsA-induced elevation of both zonula occludens-1 (ZO-1) and cholesterol in tight junctions. In contrast, a high concentration of CsA induced apoptosis which was also attenuated by lovastatin, elevated intracellular reactive oxygen species (ROS) via activation of an NADPH oxidase, and increased the expression of p47phox. Sustained treatment of the cells with lovastatin also induced significant apoptosis which was attenuated by CsA, but did not elevate intracellular ROS. These results indicate that both CsA and lovastatin are harmful t...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research