Involvement of ERK and p38 MAP kinase in oxidative stress-induced phospholipase D activation in PC12 cells

Exposure to hydrogen peroxide induced considerable activation of phospholip ase D (PLD) in rat pheochromocytoma PC12 cells. This PLD activation was pot entiated by orthovanadate and okadaic acid, suggesting that tyrosine kinase and serine/threonine kinase are involved. Furthermore, H2O2-induced PLD ac tivation was partially inhibited by either MEKI inhibitor (PD98059) or p38 MAP kinase inhibitor (SB203580), but a combination of both inhibitors resul ted in nearly 80% suppression. The major isozyme was found to be PLD2 in PC 12 cells by Western blotting analysis. When the PLD2-transfected COS-7 cell s were exposed to H2O2, the PLD activation was markedly inhibited by the co mbined pretreatment with PD98059 and SB203580. To our knowledge, this study is the first demonstration that both ERK1/2 and p38 MAP kinase are involve d in the PLD2 activation in PC12 cells exposed to H2O2. NeuroReport 12:2271 -2275 (C) 2001 Lippincott Williams & Wilkins.