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Ceramide induces apoptosis via CPP32 activation.

N Mizushima·R Koike·H Kohsaka·Y Kushi·S Handa·H Yagita·N Miyasaka
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Abstract

Although both ceramide and interleukin-1beta 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 anti-Fas- 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.

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ApoptosisCaspase 1Caspase 3CaspasesCeramidesCysteine EndopeptidasesDose-Response Relationship, DrugEnzyme InhibitorsEnzyme PrecursorsHumansJurkat CellsKineticsOligopeptidesProtease InhibitorsSphingosineJournal Article

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N Mizushima, R Koike, H Kohsaka, Y Kushi, S Handa, H Yagita, N Miyasaka. 1996-10-21. Ceramide induces apoptosis via CPP32 activation.. https://doi.org/10.1016/0014-5793(96)01050-2

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