Secretory phospholipase A2 induces apoptosis via a mechanism involving ceramide generation

被引:27
作者
Zhao, S
Du, XY
Chai, MQ
Chen, JS
Zhou, YC
Song, JG
机构
[1] Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China
[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | 2002年 / 1581卷 / 03期
基金
中国国家自然科学基金;
关键词
apoptosis; ceramide; phospholipase D; secretory phospholipase A(2); sphingomyelinase; sphingomyelin;
D O I
10.1016/S1388-1981(02)00122-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Secretory phospholipase A(2) (sPLA(2)) plays important roles in cellular signaling and various biological events. In this study, we examined the biological effects and the potential signaling mechanism of purified sPLA(2) in MV 1 Lu cells. Three types of snake venom sPLA(2) were purified and their enzymatic activities were characterized by using various lipid substrates prepared from [H-3]-myristate-labeled cells and by determining their effects on the induction of arachidonic acid (AA) release. The purified sPLA, induced apoptosis in Mv 1 Lu cells in a dose- and time-dependent manner, and was associated with a rapid increase in the intracellular ceramide level. Similar apoptotic effects were observed in Mv I Lit cells treated with exogenous ceramide analog, C-2- and C-8-ceramide. Moreover, treatment of cells with sphingomyelinase (SMase), which reduced the intracellular SM level, enhanced the apoptotic response to sPLA(2)s. sPLA(2)s also displayed an inhibitory effect on bradykinin-induced phospholipase D (PLD) activity, which can be imitated by exogenous ceramide. Our data indicate that sPLA(2) induces cell apoptosis via a mechanism involving increased ceramide generation. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:75 / 88
页数:14
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