Transient receptor potential melastatin type 7 channels are involved in zinc-induced apoptosis in gastric cancer

Abstract

Transient receptor potential melastatin 7 (TRPM7) channels are novel Ca2+-permeable non-selective cation channels that are ubiquitously expressed. Activation of TRPM7 channels has been shown to be involved in the survival of gastric cancer cells. Here we show evidence suggesting that TRPM7 channels play an important role in Zn2+-mediated cellular injury. Using a combination of electrophysiology, pharmacological analysis, small interfering RNA (siRNA) methods and cell death assays, we showed that activation of TRPM7 channels augmented Zn2+-induced apoptosis of AGS cells, the most common human gastric adenocarcinoma cell line. The Zn2+-mediated cytotoxicity was inhibited by the non-specific TRPM7 blockers Gd3+ or 2 aminoethoxydiphenyl borate (2-APB) and TRPM7 specific siRNA. In addition, we showed that overexpression of TRPM7 channels in HEK293 cells increased Zn2+-induced cell injury. Thus, TRPM7 channels may represent a novel target for physiological disorders where Zn2+toxicity plays an important role.