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

Phospholipase D (PLD) plays an important role as an effector in the membran e lipid-mediated signal transduction, However, the precise physiological fu nctions 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 p heochromocytoma (PC12) cells. Treatment of PC12 cells with H2O2 resulted in induction of apoptosis in these cells, which is accompanied by the activat ion of PLD. This H2O2-induced apoptosis was enhanced remarkably when phosph atidic 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-depen dent manner. Concomitant with PLD activation, the PLD2 activity suppressed H2O2-induced apoptosis in PC12 cells. Expression of PLD2 lipase-inactive mu tant (K758R) had no effect on either PLD activity or apoptosis, PLD2 activi ty also suppressed H2O2-induced cleavage and activation of caspase-3, Taken together, the results suggest that PLD2 activity is specifically up-regula ted by H2O2 in PC12 cells and that it plays a suppressive role in H2O2 indu ced apoptosis.