Killing of T lymphocytes by synthetic ceramide is by a nonapoptotic mechanism and is abrogated following mitogenic activation. |
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Authors: | K Mengubas A A Fahey J Lewin A B Mehta A V Hoffbrand R G Wickremasinghe |
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Affiliation: | Department of Haematology, Royal Free and University College Medical School, Rowland Hill Street, London, NW3 2PF, United Kingdom. |
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Abstract: | Ceramide induces apoptosis in leukemia cell lines and has been proposed as a potential therapeutic agent in malignancies refractory to conventional treatment. Here we show that synthetic N-acetyl-d-erythro-sphingosine (C2 ceramide) kills normal human T lymphocytes by a caspase-independent nonapoptotic mechanism. By contrast, T cells were induced to caspase-dependent apoptosis by okadaic acid. Furthermore, C2 ceramide treatment of the Jurkat leukemia cell line induced killing by apoptosis. Activation of T lymphocytes by phytohemagglutinin abrogated killing by C2 ceramide. The data here suggest that ceramide triggers caspase-dependent apoptosis in leukemia cells lines, but activates caspase-independent nonapoptotic killing of resting T lymphocytes which is abrogated following mitogenic activation. |
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