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 phospholipase D (PLD) in rat pheochromocytoma PC12 cells. This PLD activation was potentiated by orthovanadate and okadaic acid, suggesting that tyrosine kinase and serine/threonine kinase are involved. Furthermore, H2O2-induced PLD activation was partially inhibited by either MEK1 inhibitor (PD98059) or p38 MAP kinase inhibitor (SB203580), but a combination of both inhibitors resulted in nearly 80% suppression. The major isozyme was found to be PLD2 in PC12 cells by Western blotting analysis. When the PLD2-transfected COS-7 cells were exposed to H2O2, the PLD activation was markedly inhibited by the combined pretreatment with PD98059 and SB203580. To our knowledge, this study is the first demonstration that both ERK1/2 and p38 MAP kinase are involved in the PLD2 activation in PC12 cells exposed to H2O2.
Banno
Y
Y
Department of Biochemistry, Gifu University School of Medicine, Tsukasamachi-40, Gifu 500-8705, Japan.
Wang
S
S
Ito
Y
Y
Izumi
T
T
Nakashima
S
S
Shimizu
T
T
Nozawa
Y
Y
D000818:Animals; D019556:COS Cells; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D010739:Phospholipase D / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D016877:Oxidants; D011725:Pyridines; D006861:Hydrogen Peroxide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C105606:phospholipase D2; D010739:Phospholipase D; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one