Anti-apoptotic role of phospholipase D isozymes in the glutamate-induced cell death.
Phospholipase D (PLD) plays an important role as an effector in a variety of physiological processes that reveal it to be a member of the signal transducing phospholipases. Recently, PLD2 was reported as a necessary intermediate in preventing apoptosis induced by hydrogen peroxide or hypoxia in rat pheochromocytoma (PC12) cells. The data presented here show that both PLD isozymes, PLD1 and PLD2 are also required in attenuating glutamate-induced cell death in PC12 cells. Treatment of PC12 cells with glutamate resulted in induction of apoptosis in these cells, which is accompanied by decreased PLD activity and increased ceramide concentration. Incubation of PC12 cells with exogenous C6-ceramide showed a time-dependent decrease of PLD activity. When cDNAs of PLD1 and PLD2 were transfected into PC12 cells respectively, overexpression of PLD1 or PLD2 resulted in inhibition of glutamate-induced apoptotic cell death. These data indicate that both PLD1 and PLD2 play a protective role against glutamate-induced cell death in PC12 cells.
Kim
Kyung-Ok
KO
Institute of Biomedical Science and Department of Biochemistry, College of Medicine, Hanyang University, Seoul 133-791, Korea.
Lee
Kweon-Haeng
KH
Kim
Young-Hoon
YH
Park
Seung-Kiel
SK
Han
Joong-Soo
JS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity*; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D016716:PC12 Cells; D010739:Phospholipase D / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013107:Sphingolipids / Q000378:metabolism
D002518:Ceramides; D007527:Isoenzymes; D013107:Sphingolipids; C101954:N-caproylsphingosine; D018698:Glutamic Acid; D010739:Phospholipase D