We next investigated whether TRPM2 activation was ROS-dependent. Depletion of PM-induced ROS by NAC (5 mM, 1 hr pretreatment) significantly prevented PMmediated calcium influx ( Figure 3D ). Under oxidative stress, Poly ADP ribose polymerase (PARP) generates ADPribose [23, 24] , which activates TRPM2 by binding to its carboxyl terminus. The PARP inhibitor 3-aminobenzamide (3-AB, 1 mmol/L, 1 hr pretreatment)significantly reduced PM-induced Ca 2+ influx ( Figure 3E ), which further confirmed that TRPM2 is activated by PM via ROS and PARP.