FEBS Letters | |
CPP32 inhibition prevents Fas‐induced ceramide generation and apoptosis in human cells | |
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
【 预 览 】
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