We studied the inhibition of tumour necrosis factor α (TNFα)- and camptothecin-induced apoptosis by Bcl-2 and Bcl-xL as they relate to the ceramide pathway. Expression of either Bcl-2 or Bcl-xL provided significant protection from the apoptotic effects of TNFα or camptothecin. In contrast to Bcl-2, Bcl-xL overexpression did not protect cells from ceramide-induced apoptosis. On the other hand, Bcl-xL prevented the accumulation of endogenous ceramide in response to TNFα or camptothecin, whereas Bcl-2 showed little effect on ceramide formation. Moreover, Bcl-xL, but not Bcl-2, totally inhibited a caspase-8-like activity in cell lysates stimulated with TNFα. These results identify a different mechanism of action for Bcl-xL compared with Bcl-2 and they demonstrate that Bcl-xL targets a point upstream of ceramide generation, whereas Bcl-2 functions downstream of ceramide in the TNFα- and camptothecin-activated pathways of apoptosis.
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December 1998
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Research Article|
December 15 1998
Distinct sites of action of Bcl-2 and Bcl-xL in the ceramide pathway of apoptosis
Wissal EL-ASSAAD;
Wissal EL-ASSAAD
*American University of Beirut Medical Center, Department of Pediatrics, P.O. Box 113/6044, B21, Beirut, Lebanon
†Department of Biochemistry, American University of Beirut, P.O. Box 113/6044, Beirut, Lebanon
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Marwan EL-SABBAN;
Marwan EL-SABBAN
‡Department of Human Morphology, American University of Beirut, P.O. Box 113/6044, Beirut, Lebanon
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Christian AWARAJI;
Christian AWARAJI
¶Department of Pathology, American University of Beirut, P.O. Box 113/6044, Beirut, Lebanon
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Nour ABBOUSHI;
Nour ABBOUSHI
†Department of Biochemistry, American University of Beirut, P.O. Box 113/6044, Beirut, Lebanon
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Ghassan S. DBAIBO
Ghassan S. DBAIBO
1
*American University of Beirut Medical Center, Department of Pediatrics, P.O. Box 113/6044, B21, Beirut, Lebanon
†Department of Biochemistry, American University of Beirut, P.O. Box 113/6044, Beirut, Lebanon
1To whom correspondence should be sent, at the American University of Beirut Medical Center (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
June 12 1998
Revision Received:
September 02 1998
Accepted:
October 08 1998
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1998
1998
Biochem J (1998) 336 (3): 735–741.
Article history
Received:
June 12 1998
Revision Received:
September 02 1998
Accepted:
October 08 1998
Citation
Wissal EL-ASSAAD, Marwan EL-SABBAN, Christian AWARAJI, Nour ABBOUSHI, Ghassan S. DBAIBO; Distinct sites of action of Bcl-2 and Bcl-xL in the ceramide pathway of apoptosis. Biochem J 15 December 1998; 336 (3): 735–741. doi: https://doi.org/10.1042/bj3360735
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