凋亡神经酰胺途径中Bcl-2和Bcl-xL的不同作用位点。
Distinct sites of action of Bcl-2 and Bcl-xL in the ceramide pathway of apoptosis.
作者信息
El-Assaad W, El-Sabban M, Awaraji C, Abboushi N, Dbaibo G S
机构信息
American University of Beirut Medical Center, Department of Pediatrics, P.O. Box 113/6044, B21, Beirut, Lebanon.
出版信息
Biochem J. 1998 Dec 15;336 ( Pt 3)(Pt 3):735-41. doi: 10.1042/bj3360735.
Abstract
We studied the inhibition of tumour necrosis factor alpha (TNFalpha)- 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 TNFalpha 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 TNFalpha 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 TNFalpha. 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 TNFalpha- and camptothecin-activated pathways of apoptosis.
摘要
我们研究了Bcl-2和Bcl-xL对肿瘤坏死因子α（TNFα）和喜树碱诱导的细胞凋亡的抑制作用，以及它们与神经酰胺途径的关系。Bcl-2或Bcl-xL的表达对TNFα或喜树碱的凋亡效应均提供了显著的保护作用。与Bcl-2不同，Bcl-xL的过表达并不能保护细胞免受神经酰胺诱导的凋亡。另一方面，Bcl-xL可阻止内源性神经酰胺因TNFα或喜树碱而积累，而Bcl-2对神经酰胺的形成几乎没有影响。此外，Bcl-xL而非Bcl-2可完全抑制TNFα刺激的细胞裂解物中的一种类caspase-8活性。这些结果揭示了Bcl-xL与Bcl-2不同的作用机制，并且表明在TNFα和喜树碱激活的凋亡途径中，Bcl-xL作用于神经酰胺生成的上游位点，而Bcl-2则作用于神经酰胺的下游。
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