Exp Neurobiol 2004; 13(1): 21-27

Published online July 1, 2004

© The Korean Society for Brain and Neural Sciences

N-ethylmaleimide-Induced Death of Astrocytes:A Cytotoxic Role of Na+ and Cl-

Hyun-Soo Kim, HuaZi Piao and Won-Ki Kim*

Department of Pharmacology, College of Medicine; Ewha Institute ofNeuroscience, Ewha Women's University, Seoul, South Korea

Correspondence to: *To whom correspondence should be addressed.
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N-ethylmaleimide (NEM), which is experimentally used to alkylate the sulfhydryl groups, has been shown to induce cytotoxicity in various kinds of cells. Our preliminary experiments showed that NEM induced cytotoxicity in primary cultured astrocytes. In the present study, we investigated the mechanism for NEM-induced cytotoxicity in astro-cytes. NEM markedly depolarized the mitochondrial transmembrane potential. The mitochondrial permeability transition inhibitor Cyclosporin A completely blocked the NEM-evoked depolarization of mitochondrial transmembrane potential, but did not reduce the cytotoxicity of NEM. NEM also depolarized the plasma membrane potential. Removal of extracellular Na+ prevented NEM-evoked depolarization of plasma membrane potential and eliminated the cytotoxicity of NEM. Removal of extracellular Cl- also protected the NEM-induced death of astrocytes, but with no blockade of NEM-evoked depolarization of plasma membrane potential. The present study suggested that both Na+ and Cl- play a critical role in NEM-induced astrocyte death regardless of the plasma membrane potential.

Keywords: N-ethylmaleimide (NEM), LDH, astrocytes, Na+, Cl-, plasma membrane potential (PMP), mitochondrial transmembrane potential (MTP), death