A key role for Mg(2+) in TRPM7's control of ROS levels during cell stress.

The Biochemical Journal
Hsiang-Chin ChenL W Runnels

Abstract

The TRPM7 (transient receptor potential melastatin 7) channel has been shown to play a pivotal role in cell survival during brain ischaemia as well as in the survival of other cell types challenged with apoptotic stimuli. Ca(2+) is thought to be central to the channel's ability to regulate ROS (reactive oxygen species) production. However, channel-mediated entry of Mg(2+) and Zn(2+) have also been implicated in cell death. In the present study, we show that depletion of TRPM7 by RNA interference in fibroblasts increases cell resistance to apoptotic stimuli by decreasing ROS levels in an Mg(2+)-dependent manner. Depletion of TRPM7 lowered cellular Mg(2+), decreased the concentration of ROS and lessened p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase) activation as well as decreased caspase 3 activation and PARP [poly(ADP-ribose) polymerase] cleavage in response to apoptotic stimuli. Re-expression of TRPM7 or of a kinase-inactive mutant of TRPM7 in TRPM7-knockdown cells increased cellular Mg(2+) and ROS levels, as did expression of the Mg(2+) transporter SLC41A2 (solute carrier family 41 member 2). In addition, expression of SLC41A2 increased the sensitivity of TRPM7-knockdown cells to apoptotic stimu...Continue Reading

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Citations

Nov 22, 2013·World Journal of Urology·Zhe MengXinghuan Wang
Jul 29, 2015·Channels·Yuyang SunBrij B Singh
Sep 1, 2015·Biochimica Et Biophysica Acta·Yutaka ShindoKotaro Oka
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Aug 5, 2018·The Journal of Biological Chemistry·Yan HuangZhi-Gang Xiong
Apr 22, 2020·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Loren W Runnels, Yuko Komiya

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