CPP32 inhibition prevents Fas‐induced ceramide generation and apoptosis in human cells
- 22 July 1996
- journal article
- Published by Wiley in FEBS Letters
- Vol. 390 (2) , 233-237
- https://doi.org/10.1016/0014-5793(96)00666-7
Abstract
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.Keywords
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