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.
Distinct sites of action of Bcl-2 and Bcl-xL in the ceramide pathway of apoptosis
- Views Icon Views
- PDF LinkPDF
- Share Icon Share
- Cite Icon Cite
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
Download citation file: