Roles of TRPM2 in oxidative stress

Reactive oxygen species (ROS) play critical roles in cell death, diseases, and normal cellular processes. TRPM2 is a member of transient receptor potential (TRP) protein superfamily and forms a Ca2+-permeable nonselective cation channel activated by ROS, specifically by hydrogen peroxide (H2O2), and at least in part via second-messenger mechanisms. Accumulating evidence has indicated that TRPM2 mediates multiple cellular responses, after our finding that Ca2+ influx via TRPM2 regulates H2O2-induced cell death. Recently, we have demonstrated that Ca2+ influx through TRPM2 induces chemokine production in monocytes and macrophages, which aggravates inflammatory neutrophil infiltration in mice. However, understanding is still limited for in vivo physiological or pathophysiological significance of ROS-induced TRPM2 activation. In this review, we summarize mechanisms underlying activation of TRPM2 channels by oxidative stress and downstream biological responses, and discuss the biological importance of oxidative stress-activated TRP channels. (C) 2011 Elsevier Ltd. All rights reserved.