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CPP32 inhibition prevents Fas‐induced ceramide generation and apoptosis in human cells
Author(s) -
Gamen Susana,
Marzo Isabel,
Anel Alberto,
Piñeiro Andrés,
Naval Javier
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)00666-7
Subject(s) - ceramide , jurkat cells , apoptosis , intracellular , microbiology and biotechnology , sphingomyelin , u937 cell , protease , lipid signaling , chemistry , proteases , programmed cell death , biology , biochemistry , enzyme , t cell , immunology , immune system , membrane
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.