Compound C inhibits hypoxic activation of HIF-1 independent of AMPK

被引：93

作者：

Emerling, Brooke M. ^{[1
,4
]}

Viollet, Benoit ^{[2
,3
]}

Tormos, Kathryn V. ^{[4
]}

Chandel, Navdeep S. ^{[4
]}

机构：

[1] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA

[2] Univ Paris 05, Inst Cochin, CNRS, UMR 8104, Paris, France

[3] INSERM, U567, Paris, France

[4] Northwestern Univ, Dept Med, Chicago, IL 60611 USA

来源：

FEBS LETTERS | 2007年 / 581卷 / 29期

关键词：

hypoxia inducible factor 1; AMP-activated kinase; compound C; hypoxia; mitochondria; reactive oxygen species;

D O I：

10.1016/j.febslet.2007.11.038

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：

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.

引用

页码：5727 / 5731

页数：5

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