期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 275, 期 24, 页码 18099-18107出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M908925199
关键词
-
Tumor necrosis factor (TNF) does not cause endothelial apoptosis unless the expression of cytoprotective genes is blocked. We have previously demonstrated that one of the TNF-inducible cytoprotective genes is the Bcl-2 family member, Al. Al is induced by the action of the transcription factor, NF kappa B, in response to inflammatory mediators. In this report we demonstrate that, as with other cell types, inhibition of NF kappa B initiates microvascular endothelial apoptosis in response to TNF. Al is able to inhibit this apoptosis over 24 h, We demonstrate that Al is localized to and functions at the mitochondria. Whereas Al is able to inhibit mitochondrial depolarization, loss of cytochrome c, cleavage of caspase 9, BID, and poly(ADP-ribose) polymerase, it does not block caspase 8 or caspase 3 cleavage. In contrast, Al is not able to prevent endothelial apoptosis by TNF over 72 h, when NF kappa B signaling is blocked. On the other hand, the caspase inhibitor, benzyloxycarbonyl-VAD-formylmethyl ketone, completely blocks TNF-induced endothelial apoptosis over 72 h. Our findings indicate that Al is able to maintain temporary survival of endothelial cells in response to TNF by maintaining mitochondrial viability and function. However, a mitochondria-independent caspase pathway eventually results in endothelial death despite mitochondrial protection by A1.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据