期刊
FEBS LETTERS
卷 581, 期 29, 页码 5727-5731出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2007.11.038
关键词
hypoxia inducible factor 1; AMP-activated kinase; compound C; hypoxia; mitochondria; reactive oxygen species
资金
- NCI NIH HHS [R01 CA123067, R01 CA123067-01A1, CA123067-01] Funding Source: Medline
- NIGMS NIH HHS [R01 GM060472, R01 GM060472-08, GM60472-08] Funding Source: Medline
The key transcription factor that regulates the cellular responses to hypoxia is hypoxia inducible factor-1 (HIF-1). The signaling mechanisms that regulate the hypoxic activation of HIF-1 are not fully understood. Our objective here was to test whether AMP-activated kinase (AMPK) was an upstream regulator of HIF-1. Our results show that AMPK is not required for the hypoxic activation of HIF-1. Interestingly, the AMPK inhibitor, Compound C, inhibits the hypoxic activation of HIF-1 independent of AMPK. Furthermore, we demonstrate that Compound C functions as a repressor of HIF-1 by inhibiting respiration and suppressing mitochondrial generated ROS. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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