Melatonin modulates apoptosis and TRPM2 channels in transfected cells activated by oxidative stress

Transient receptor potential melastatin-like 2 (TRPM2) is a non-selective Ca2+ permeable cation channel and is known to be activated by H2O2, one of the most important indicators of intracellular oxidative stress. A neurohormone melatonin may have a modulator role on TRPM2 channels activated by oxidative stress because it is a strong antioxidant. In this study we investigated the effects of melatonin on apoptosis, whole cell currents and Ca2+ influx arising from TRPM2 channels activated by H2O2. In whole-cell patch clamp experiments, TRPM2 channels in transfected Chinese hamster ovary (CHO) cells were activated by H2O2. However, the currents were inhibited either by intracellular or by extracellular melatonin. When intracellular melatonin was introduced by pipette, TRPM2 channel currents were not activated by H2O2 although H2O2-induced Ca2+ gating and release were not blocked 2-aminoethyldiphenyl borate (2-APB). Cytosolic Ca2+ release was measured by Fura-2 and was higher in H2O2 groups than in control. Melatonin also inhibited apoptosis in the transfected cells. In conclusion, we observed modulator roles of intracellular and extracellular melatonin on Ca2+ influx and apoptosis through a TRPM2 channel in transfected CHO cells. (C) 2012 Elsevier Inc. All rights reserved.