Regulation by sphingosine 1-phosphate of Bax and Bad activities during apoptosis in a MEK-dependent manner

被引：36

作者：

Betito, S ^{[1
]}

Cuvillier, O ^{[1
]}

机构：

[1] Inst Louis Bugnard, INSERM, U466, F-31432 Toulouse 4, France

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2006年 / 340卷 / 04期

关键词：

sphingosine l-phosphate; Bax; Bad; Fas; mitochondria; apoptosis; ERK; cytochrome c;

D O I：

10.1016/j.bbrc.2005.12.138

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：

Herein we report that the prosurvival sphingolipid sphingosine 1-phosphate regulates the activities of both Bad and Bax during apoptosis of Jurkat cells. First, sphingosine 1-phosphate treatment results in Bad inactivation via the ERK/Rsk-1 pathway. Second, sphingosine 1-phosphate blocks the translocation of Bax to the mitochondria induced by Fas ligation. MEK inhibition by PD98059 or U0126 not only abrogates sphingosine I-phosphate-induced Bad phosphorylation, but also its cytoprotective effect. Furthermore, inhibition of both mitochondrial cytochrome c efflux and Bax translocation to the mitochondria by sphingosine I-phosphate could be overcome by PD98059 or U0126. Hence, the MEK/ERK pathway seems to be crucial for the survival effects initiated by sphingosine I-phosphate. (c) 2006 Elsevier Inc. All rights reserved.

引用

页码：1273 / 1277

页数：5

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