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KMID : 0811720000040000009
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Korean Journal of Physiology & Pharmacology
2000 Volume.4 No. 0 p.9 ~ p.0
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Regulation of Phospholipase D2 by H2O2 in PC12 Cells
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Oh Sae-Ock
Hong Jang-Hee
Yoo Hyang-Sook
Lee Sang-Ho
Im Kyu
Hwang Byung-Doo
Exton John H.
Park Seung-Gil
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Abstract
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Phospholipase D2 (PLD2) is expressed in brain and inhibited by synuclein, which is involved in Parkinson’s and Alzheimer’s diseases. However the activation mechanism of PLD2 in neuronal cells has not been defined clearly. Hydrogen peroxide (H2O2) plays roles in the neurodegenerative diseases and also acts as a second messenger of various molecules such as nerve growth factor. To study regulation mechanisms of PLD2 by H2O2 in neuronal cell, we have made stable PC12 cell lines expressing PLD2 (PLD2-PC12 cell). H2O2 treatment stimulated PLD activity in PLD2-PC12 cells in a dose- and time-dependent manner. This activation was inhibited by the treatment of protein kinase C (PKC) inhibitors or by depletion of PKC, and phorbol ester markedly activated PLD2. Co-treatment with phorbol ester and H2O2 did not show an additive effect. Chelation of extracellular calcium substantially blocked the H2O2-induced activation of PLD2. A calcium ionophore induced PLD2 activation in PKC-dependent manner. Protein-tyrosine kinase inhibitors inhibited H2O2-induced PLD activation slightly. These data indicate that H2O2 can activate PLD2 in PC12 cells and that this activation is largely dependent on PKC and Ca2+ ions, and minimally dependent on tyrosine phosphorylation. Published in Journal of Neurochemistry in press: Supported by Korea Research Foundation Grant (KRF-99-015-DP0313).
Source: Korean Journal of Physiology & Pharmacology.2000 Oct;4(Suppl):S14-S14
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