A non-hypoxic, ROS-sensitive pathway mediates TNF-α-dependent regulation of HIF-1α

被引：222
作者：
Haddad, JJ [1 ]
Land, SC [1 ]
机构：
[1] Univ Dundee, Ninewells Hosp & Med Sch, Fac Med, Tayside Inst Child Hlth,Oxygen Signaling Grp, Dundee DD1 9SY, Scotland
来源：
FEBS LETTERS | 2001年 / 505卷 / 02期
基金：
英国医学研究理事会; 英国惠康基金;
关键词：
antioxidant; hypoxia-inducible factor-1 alpha; mitochondrion; oxygen sensing; reactive oxygen species; tumor necrosis factor-alpha;
D O I：
10.1016/S0014-5793(01)02833-2
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：
A non-hypoxic, reactive oxygen species (ROS)sensitive pathway mediating tumor necrosis factor-alpha (TNF-alpha )dependent regulation of hypoxia-inducible factor-1 alpha (HIF-alpha) was investigated in vitro. TNF-alpha mediated the translocation of HIF-1 alpha, associated with up-regulating its activity under normoxia. Analysis of the mode of action of TNF-alpha revealed the accumulation of hydrogen peroxide (H2O2), superoxide anion (O-2(-.)) and hydroxyl radical ((OH)-O-.). Antioxidants purported as prototypical scavengers of H2O2 and (OH)-O-., attenuated TNF-alpha -induced HIF-1 alpha activation, and blockading NADPH-oxidase by scavenging O-2(.) reduced the activity of HIF-1 alpha. Inhibition of the mitochondrion complex I abrogated TNF-alpha -dependent activation of HIF-1 alpha. Interrupting the respiratory chain reversed the excitatory effect of TNF-alpha on HIF-1 alpha. These results indicate a non-hypoxic pathway mediating cytokine-dependent regulation of HIF-1 alpha in a ROS-sensitive mechanism. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码：269 / 274
页数：6
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