Lovastatin Attenuates Effects of Cyclosporine A on Tight Junctions and Apoptosis in Cultured Cortical Collecting Duct Principal Cells

Overview

Journal Am J Physiol Renal Physiol

Publisher American Physiological Society

Specialties Nephrology
Physiology

Date 2013 May 31

PMID 23720343

Citations 8

Authors

Bing-Chen Liu

Xiang Song

Xiao-Yu Lu

Charles Z Fang

Shi-Peng Wei

Abdel A Alli

Douglas C Eaton

Bao-Zhong Shen

Xue-Qi Li

He-Ping Ma

Affiliations

Soon will be listed here.

Abstract

We used mouse cortical collecting duct principal cells (mpkCCDc14 cell 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 cells with CsA increased transepithelial resistance and that the effect of CsA was abolished by lovastatin. Scanning ion conductance microscopy 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 cells. Western blot analysis and confocal microscopy showed that lovastatin also abolished CsA-induced elevation of both zonula occludens-1 and cholesterol in tight junctions. In contrast, a high concentration of CsA induced apoptosis, which was also attenuated by lovastatin, elevated intracellular ROS via activation of NADPH oxidase, and increased the expression of p47phox. Sustained treatment of 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 to principal cells of the distal tubule, but via ROS-dependent and ROS-independent apoptotic pathways, respectively, and that they counteract probably via mobilization of cellular cholesterol levels.

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