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Killing of T lymphocytes by synthetic ceramide is by a nonapoptotic mechanism and is abrogated following mitogenic activation

Mengubas, K; Fahey, AA; Lewin, J; Mehta, AB; Hoffbrand, AV; Wickremasinghe, RG; (1999) Killing of T lymphocytes by synthetic ceramide is by a nonapoptotic mechanism and is abrogated following mitogenic activation. EXP CELL RES , 249 (1) 116 - 122.

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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-Derythro-sphingosine (C-2 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, C-2 ceramide treatment of the Jurkat leukemia cell line induced killing by apoptosis. Activation of T lymphocytes by phytohemagglutinin abrogated killing by C-2 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. (C) 1999 Academic Press.

Type: Article
Title: Killing of T lymphocytes by synthetic ceramide is by a nonapoptotic mechanism and is abrogated following mitogenic activation
Keywords: apoptosis, T lymphocyte, cell cycle, ceramide, caspase, okadaic acid, RADIATION-INDUCED APOPTOSIS, SPHINGOMYELINASE-DEFICIENT MICE, TUMOR-NECROSIS-FACTOR, NIEMANN-PICK DISEASE, NECROTIC CELL-DEATH, PROTEIN-KINASE, DNA-DAMAGE, REQUIREMENT, RESISTANCE, INHIBITION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/121913
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