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PubMed · 8456305

Programmed cell death induced by ceramide.

L M Obeid·C M Linardic·L A Karolak·Y A Hannun
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Abstract

Sphingomyelin hydrolysis and ceramide generation have been implicated in a signal transduction pathway that mediates the effects of tumor necrosis factor-alpha (TNF-alpha) and other agents on cell growth and differentiation. In many leukemic cells, TNF-alpha causes DNA fragmentation, which leads to programmed cell death (apoptosis). C2-ceramide (0.6 to 5 microM), a synthetic cell-permeable ceramide analog, induced internucleosomal DNA fragmentation, which was inhibited by zinc ion. Other amphiphilic lipids failed to induce apoptosis. The closely related C2-dihydroceramide was also ineffective, which suggests a critical role for the sphingolipid double bond. The effects of C2-ceramide on DNA fragmentation were prevented by the protein kinase C activator phorbol 12-myristate 13-acetate, which suggests the existence of two opposing intracellular pathways in the regulation of apoptosis.

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ApoptosisCeramidesDNADNA DamageLeukemiaNucleosomesProtein Kinase CSphingomyelinsTetradecanoylphorbol AcetateTumor Cells, CulturedTumor Necrosis Factor-alphaZincJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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L M Obeid, C M Linardic, L A Karolak, Y A Hannun. 1993-03-19. Programmed cell death induced by ceramide.. https://doi.org/10.1126/science.8456305

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