CPP32 inhibition prevents Fas‐induced ceramide generation and apoptosis in human cells

FEBS Letters

Naval, Javier¹  Marzo, Isabel¹  Piñeiro, Andrés¹  Gamen, Susana¹  Anel, Alberto¹ 

[1] Departamento de Bioquímica y Biologia Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain

关键词: Fas;    Tumor necrosis factor α;    Ceramide;    ICE-like proteases;    Apoptosis;    TNF;    tumor necrosis factor α;    anti-Fas;    cytotoxic monoclonal anti-Fas antibody;    ICE;    interleukin-1β-converting enzyme;    PARP;    poly(ADP-ribose) polymerase;    MTT;    3-[4;    5-dimethylthiazol-2-yl]-2;    5-diphenyl-tetrazolium bromide;    C2-ceramide;    N-acetyl-ceramide;    C18-ceramide;    N-octadecanoyl-ceramide;    PPDA;    p-phenylenediamine;   

DOI  :  10.1016/0014-5793(96)00666-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Intracellular activation of sphingomyelinase, leading to ceramide generation, and ICE-like proteases have been implicated in TNF and Fas-induced apoptosis, but the links between these intracellular apoptotic mediators remain undefined. We show here that a specific peptide inhibitor of the ICE-like protease CPP32/Yama (DEVD-cho) blocks anti-Fasinduced apoptosis in Jurkat and U937 cells, while having no effect on TNF-induced apoptosis in U937 cells. This peptide also prevents ceramide accumulation induced by Fas engagement. Jurkat and U937 cells, as well as their mtDNA-depleted derived lines (π° cells), were sensitive to ceramide toxicity, which was not prevented by ICE-like protease inhibitors. These results, taken together, suggest that ICE-like protease activation is a prerequisite for ceramide generation and subsequent apoptosis, at least in the case of Fas-induced cell death.

【 授权许可】

Unknown