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Ceramide induces apoptosis via CPP32 activation
Author(s) -
Mizushima Noboru,
Koike Ryuji,
Kohsaka Hitoshi,
Kushi Yasunori,
Handa Shizuo,
Yagita Hideo,
Miyasaka Nobuyuki
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)01050-2
Subject(s) - ceramide , jurkat cells , apoptosis , sphingomyelin , lipid signaling , microbiology and biotechnology , chemistry , proteases , protease , biochemistry , biology , enzyme , t cell , immunology , immune system , membrane
Although both ceramide and interleukin‐1β 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 antiFas‐ 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.