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    Evidence against an early signalling role for ceramide in Fas-mediated apoptosis

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    Date
    1997
    Author
    Sillence, Daniel J.;
    Allan, D.
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    Abstract
    We have investigated whether the increases in ceramide levels that occur during apoptosis in SKW 6.4 cells induced by anti-Fas antibody depend on the activation of caspases. Using cells prelabelled to equilibrium with [14C]acetate, it was shown that the amount of ceramide approximately doubled after 24 h incubation with anti-Fas, but the time course of ceramide changes was slower than that of anti-Fas-induced cell death. Complete inhibition of the effects of anti-Fas on cell death and on ceramide production was observed when the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-(O-methyl)fluoromethane (zVAD.fmk) was added together with anti-Fas, but N-benzyloxycarbonyl-Phe-Ala-fluoromethane (a structurally similar cathepsin B inhibitor) had no effect. Treatment of cells with the Ca2+-ionophore A23187 also doubled ceramide levels, but in this case the effect was complete within 2 h, was not blocked by zVAD.fmk and was not associated with increases in nuclear fragmentation. These results suggest that ceramide is not an upstream messenger in Fas-mediated apoptosis and may instead be produced as a consequence of processes downstream of the activation of caspases and increases in cytosolic calcium concentration.
    Description
    Citation : Sillence, D.J and Allan, D. (1997) Evidence against an early signalling role for ceramide in Fas-mediated apoptosis. Biochemical Journal, 324, pp. 29-32
    URI
    http://hdl.handle.net/2086/10763
    Research Institute : Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)
    Peer Reviewed : Yes
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    • Leicester School of Pharmacy [1196]

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