Ceramide induces apoptosis via CPP32 activation

FEBS Letters

Kohsaka, Hitoshi¹  Handa, Shizuo²  Koike, Ryuji⁴  Mizushima, Noboru⁴  Miyasaka, Nobuyuki⁴  Yagita, Hideo³  Kushi, Yasunori² 

[1] Division of Immunological Diseases, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113, Japan;The First Department of Biochemistry, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113, Japan;Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113, Japan;The First Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113, Japan

关键词: CPP32;    Ceramide;    Apoptosis;    Fas;    Interleukin1β converting enzyme;    ICE;    interleukin-1β converting enzyme;    SMase;    sphingomyelinase;    TNFR;    tumor necrosis factor receptor;    PARP;    poly-ADP ribose polymerase;    FCS;    feta calf serum;    AMC;    7-amino-4-methyl-coumarin;   

DOI  :  10.1016/0014-5793(96)01050-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown