Ceramide induces apoptosis via CPP32 activation

被引:125
作者
Mizushima, N
Koike, R
Kohsaka, H
Kushi, Y
Handa, S
Yagita, H
Miyasaka, N
机构
[1] TOKYO MED & DENT UNIV,MED RES INST,DIV IMMUNOL DIS,BUNKYO KU,TOKYO 113,JAPAN
[2] TOKYO MED & DENT UNIV,FAC MED,DEPT BIOCHEM 1,BUNKYO KU,TOKYO 113,JAPAN
[3] JUNTENDO UNIV,SCH MED,DEPT IMMUNOL,TOKYO 113,JAPAN
关键词
CPP32; ceramide; apoptosis; Fas; interleukin-1; beta; converting enzyme;
D O I
10.1016/0014-5793(96)01050-2
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
Although both ceramide and interleukin-1 beta converting enzyme (ICE) family proteases are key molecules during apoptosis, their relationship remains to be elucidated. We report here that cell-permeable ceramide induced cleavage and activation of CPP32, a Ced-3/ICE-like protease, but not ICE. Ceramide-induced apoptosis of Jurkat cells was blocked by the CPP32-specific tetrapeptide inhibitor DEVD-CHO, but not by the ICE inhibitor YVAD-CHO. Furthermore, variant Jurkat cells with defective CPP32 activation were resistant to both anti-Fas- and ceramide-induced apoptosis. These results indicate that CPP32 activation is required for ceramide-induced apoptosis, and suggest sphingomyelin-ceramide pathway functions upstream of CPP32.
引用
收藏
页码:267 / 271
页数:5
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