期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 275, 期 33, 页码 25130-25138出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M001914200
关键词
-
资金
- NHLBI NIH HHS [HL35440, HL32646] Funding Source: Medline
During hypoxia, hypoxia-inducible factor-1 alpha (HIF-1 alpha) is required for induction of a variety of genes including erythropoietin and vascular endothelial growth factor. Hypoxia increases mitochondrial reactive oxygen species (ROS) generation at Complex III, which causes accumulation of HIF-1 alpha protein responsible for initiating expression of a luciferase reporter construct under the control of a hypoxic response element. This response is lost in cells depleted of mitochondrial DNA (rho degrees cells). Overexpression of catalase abolishes hypoxic response element-luciferase expression during hypoxia. Exogenous H2O2 stabilizes HIF-1 alpha protein during normoxia and activates luciferase expression in wild-type and rho degrees cells. Isolated mitochondria increase ROS generation during hypoxia, as does the bacterium Paracoccus denitrificans. These findings reveal that mitochondria-derived ROS are both required and sufficient to initiate HIF-1 alpha stabilization during hypoxia.
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