Compound C inhibits hypoxic activation of HIF-1 independent of AMPK
Compound C inhibits hypoxic activation of HIF-1 independent of AMPK
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DOI：
10.1016/j.febslet.2007.11.038
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发表时间：
2007-12-11
期刊：
影响因子：
3.5
通讯作者：
Chandel, Navdeep S.
中科院分区：
文献类型：
--
作者：
Emerling, Brooke M.;Viollet, Benoit;Chandel, Navdeep S.
缺氧诱导因子-1（hypoxia inducible factor-1，HIF-1）是调节细胞缺氧反应的关键转录因子。调节HIF-1的低氧激活的信号传导机制尚未完全了解。我们的目的是测试AMP激活的激酶（AMPK）是否是HIF-1的上游调节因子。我们的研究结果表明，AMPK是不需要缺氧激活HIF-1。有趣的是，AMPK抑制剂化合物C抑制HIF-1的缺氧活化，而不依赖于AMPK。此外，我们证明化合物C通过抑制呼吸和抑制线粒体产生的ROS而作为HIF-1的阻遏物起作用。(C)2007年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
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.