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Regulation of Phospholipase D2 by H 2 O 2 in PC12 Cells
Author(s) -
Oh SaeOck,
Hong JangHee,
Kim YoungRae,
Yoo HyangSook,
Lee SangHo,
Lim Kyu,
Hwang ByungDoo,
Exton John H.,
Park SeungKiel
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0752445.x
Subject(s) - pld2 , phospholipase d , chemistry , protein kinase c , calcium , phosphorylation , kinase , microbiology and biotechnology , biochemistry , biology , signal transduction , phosphatidic acid , phospholipid , organic chemistry , membrane
Phospholipase D2 (PLD2) is expressed in brain andinhibited by synuclein, which is involved in Parkinson's and Alzheimer'sdiseases. However, the activation mechanism of PLD2 in neuronal cells has notbeen defined clearly. Hydrogen peroxide (H 2 O 2 ) playsroles in the neurodegenerative diseases and also acts as a second messenger ofvarious molecules such as nerve growth factor. To study regulation mechanismsof PLD2 by H 2 O 2 in neuronal cells, we have made stablePC12 cell lines expressing PLD2 (PLD2‐PC12 cells). H 2 O 2 treatment stimulated PLD activity in PLD2‐PC12 cells in a dose‐ andtime‐dependent manner. This activation was inhibited by the treatment withprotein kinase C (PKC) inhibitors or by depletion of PKCα, ‐δ, and‐ε. Phorbol ester markedly activated PLD2. Co‐treatment with phorbolester and H 2 O 2 did not show an additive effect.Chelation of extracellular calcium substantially blocked theH 2 O 2 ‐induced activation of PLD2. A calcium ionophoreinduced PLD2 activation in a PKC‐dependent manner. Protein‐tyrosine kinaseinhibitors inhibited H 2 O 2 ‐induced PLD activationslightly. These data indicate that H 2 O 2 can activatePLD2 in PC12 cells and that this activation is largely dependent on PKC andCa 2+ ions and minimally dependent on tyrosine phosphorylation.