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TRPC6 Channel‐Mediated Neonatal Glomerular Mesangial Cell Apoptosis Involves Activation of Calcineurin/Nuclear Factor of Activated T‐Cell Signaling
Author(s) -
Soni Hitesh,
Adebiyi Adebowale
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.784.3
Subject(s) - trpc6 , nfat , calcineurin , apoptosis , microbiology and biotechnology , trpc , chemistry , oxidative stress , signal transduction , transient receptor potential channel , cancer research , biology , medicine , receptor , transplantation , biochemistry
Alterations in glomerular mesangial cell (GMC) survival are involved in the pathogenesis of progressive glomerulopathies. However, the mechanisms that underlie GMC survival are not fully resolved. In this study, we examined whether activation of the canonical transient receptor potential (TRPC) 6 channels modulates GMC survival. Hyperforin (HF)‐induced TRPC6 channel activation elevated intracellular Ca 2+ ([Ca 2+ ] i ) concentration, inhibited proliferation, and promoted apoptosis in primary GMCs derived from newborn pig kidneys. Dichlorodihydrofluorescein diacetate assay revealed that HF‐induced GMC apoptosis is not associated with oxidative stress. However, HF‐induced GMC apoptosis was attenuated by BAPTA‐AM, a [Ca 2+ ] i chelator, Ac‐DEVD‐CHO, a caspase‐3/7 inhibitor, and siRNA‐mediated TRPC6 channel knockdown. HF also stimulated nuclear translocation of NFATC1 in the cells in a [Ca 2+ ] i ‐dependent manner. Furthermore, HF‐induced apoptosis was abrogated in GMCs pretreated with calcineurin/NFAT signaling inhibitors FK506 and 11R‐VIVIT. These findings suggest that an elevation in [Ca 2+ ] i elicited by TRPC6 channel activation promotes neonatal GMC apoptosis by activating the calcineurin/NFAT signaling pathway.