Exp Mol Med.  2003 Feb;35(1):38-45.

Anti-apoptotic role of phospholipase D isozymes in the glutamate-induced cell death

• Kim KO
• Lee KH
• Kim YH
• Park SK
• Han JS

Abstract

Abstract 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.

Keyword

apoptosis; ceramides; glutamic acid; PC12 cells; phospholipase D

MeSH Terms

Animals
Apoptosis/drug effects/*physiology
Cell Survival/drug effects
Ceramides/pharmacology
Dose-Response Relationship, Drug
Enzyme Activation
Gene Expression Regulation, Enzymologic/drug effects
Glutamic Acid/*toxicity
Isoenzymes/drug effects/genetics/*metabolism
Kinetics
PC12 Cells
Phospholipase D/chemistry/drug effects/genetics/*metabolism
Rats
Sphingolipids/metabolism