Phospholipase D2 activity suppresses hydrogen peroxide-induced apoptosis in PC12 cells

Phospholipase D (PLD) plays an important role as an effector in the membrane lipid-mediated signal transduction, However, the precise physiological functions of PLD are not yet well understood, In this study, we examined the role of PLD activity in hydrogen peroxide (H2O2)-induced apoptosis in rat pheochromocytoma (PC12) cells. Treatment of PC12 cells with H2O2 resulted in induction of apoptosis in these cells, which is accompanied by the activation of PLD. This H2O2-induced apoptosis was enhanced remarkably when phosphatidic acid production by PLD was selectively inhibited by pretreating the PC12 cells with 1-butanol, Expression of PLD2, but not of PLD1, correlated with increased H2O2 induced PLD activity in a concentration- and time-dependent manner. Concomitant with PLD activation, the PLD2 activity suppressed H2O2-induced apoptosis in PC12 cells. Expression of PLD2 lipase-inactive mutant (K758R) had no effect on either PLD activity or apoptosis, PLD2 activity also suppressed H2O2-induced cleavage and activation of caspase-3, Taken together, the results suggest that PLD2 activity is specifically up-regulated by H2O2 in PC12 cells and that it plays a suppressive role in H2O2 induced apoptosisclose484