Abstract
Abnormal mitochondrial calcium accumulation plays a critical role in oxidative stress-induced apoptosis of melanocytes. Transient receptor potential cation channel subfamily M member 2 (TRPM2) is a calcium channel sensitive to oxidative stress. However, whether TRPM2 participates in melanocyte apoptosis under oxidative stress was unknown before. In the present study, we initially found that hydrogen peroxide (H2O2) induced the demethylation of the promoter region in TRPM2 gene and increased the expression of TRPM2 in normal human melanocytes (NHMs). Meanwhile, TRPM2 was overexpressed in lesional melanocytes of vitiligo that is a skin disease caused by melanocyte loss under oxidative stress. Furthermore, either TRPM2 inhibitors or TRPM2 shRNA could ameliorate H2O2-induced apoptosis, mitochondrial reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) loss in NHMs, which was similar to the effects of an anti-oxidant. More importantly, TRPM2 mediated the calcium influx into the cytoplasm and the mitochondria of NHMs exposed to H2O2, and a specific mitochondrial Ca2+ uptake inhibitor Ruthenium 360 (Ru360) could also protect NHMs from apoptosis and mitochondrial damages caused by H2O2. Taken together, our findings demonstrate that oxidative stress promotes the expression of TRPM2 and thus facilitates mitochondria-dependent apoptosis of melanocytes by increasing calcium influx. Our study indicates that TRPM2 is a potential target for protecting melanocytes against oxidative damages in vitiligo.