Compound C prevents Hypoxia-Inducible Factor-1 protein stabilization by regulating the cellular oxygen availability via interaction with Mitochondrial Complex i

被引：6

作者：

Chua Y.L. ^{[1
]}

Hagen T. ^{[1
]}

机构：

[1] Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore

来源：

BMC Research Notes | / 4卷 / 1期

关键词：

Electron Transport Chain; Rotenone; H2O2 Production; Electron Flux; Mitochondrial Electron Transport Chain;

D O I：

10.1186/1756-0500-4-117

中图分类号：

学科分类号：

摘要：

The transcription factor Hypoxia-Inducible Factor-1 is a master regulator of the cellular response to low oxygen concentration. Compound C, an inhibitor of AMP-activated kinase, has been reported to inhibit hypoxia dependent Hypoxia-Inducible Factor-1 activation via a mechanism that is independent of AMP-activated kinase but dependent on its interaction with the mitochondrial electron transport chain. The objective of this study is to characterize the interaction of Compound C with the mitochondrial electron transport chain and to determine the mechanism through which the drug influences the stability of the Hypoxia-Inducible Factor-1 protein. We found that Compound C functions as an inhibitor of complex I of the mitochondrial electron transport chain as demonstrated by its effect on mitochondrial respiration. It also prevents hypoxia-induced Hypoxia-Inducible Factor-1 stabilization in a dose dependent manner. In addition, Compound C does not have significant effects on reactive oxygen species production from complex I via both forward and reverse electron flux. This study provides evidence that similar to other mitochondrial electron transport chain inhibitors, Compound C regulates Hypoxia-Inducible Factor-1 stability by controlling the cellular oxygen concentration. © 2011 Hagen et al; licensee BioMed Central Ltd.

引用

共 8 条

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