Hepatocyte growth factor protects against hypoxia/reoxygenation-induced apoptosis in endothelial cells

被引:62
作者
Wang, X
Zhou, YS
Kim, HP
Song, RP
Zarnegar, R
Ryter, SW
Choi, AMK
机构
[1] Univ Pittsburgh, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Med Ctr, Ctr Biotechnol & Bioengn, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Med Ctr, Dept Pathol, Div Cellular & Mol Pathol, Pittsburgh, PA 15213 USA
关键词
D O I
10.1074/jbc.M309271200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hypoxia/reoxygenation causes cellular injury and death associated with a number of pathophysiological conditions, including myocardial ischemia/reperfusion injury and stroke. The cell death pathways induced by hypoxia/reoxygenation and their underlying regulatory mechanisms remain poorly understood. Recent studies have shown that hypoxia/reoxygenation can induce Bax translocation and cytochrome c release. Using murine lung endothelial cells as a model, we found that the induction of apoptosis by hypoxia/reoxygenation involved the activation of both Bax-dependent and death receptor-mediated pathways. We demonstrated the activation of the death-inducing signal complex and Bid pathway after hypoxia/reoxygenation. Hepatocyte growth factor markedly inhibited hypoxia/reoxygenation-induced endothelial cell apoptosis. The cytoprotection afforded by hepatocyte growth factor was mediated in part by the stimulation of FLICE-like inhibiting protein expression, the attenuation of death-inducing signal complex formation, and the inhibition of Bid and Bax activation. Hepatocyte growth factor also prevented cell injury and death by increasing the expression of the antiapoptotic Bcl-X-L protein. The inhibition of Bid/Bax-induced cell death by hepatocyte growth factor primarily involved p38 MAPK and in part Akt-dependent pathways but not ERK1/ERK2.
引用
收藏
页码:5237 / 5243
页数:7
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