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缺氧诱导因子1对持续和间歇性缺氧的生理反应的调节

Regulation of physiological responses to continuous and intermittent hypoxia by hypoxia-inducible factor 1.

作者信息

Semenza Gregg L

机构信息

Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

出版信息

Exp Physiol. 2006 Sep;91(5):803-6. doi: 10.1113/expphysiol.2006.033498. Epub 2006 Jun 1.

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor composed of HIF-1alpha and HIF-1beta subunits that functions as a master regulator of oxygen homeostasis. Oxygen-dependent hydroxylation of HIF-1alpha provides a mechanism that allows changes in oxygenation to be transduced to the nucleus, leading to changes in gene expression. Hypoxia-inducible factor 1 plays critical roles in development, physiology and disease pathogenesis. Analyses of mice that are heterozygous for a null allele at the locus encoding the HIF-1alpha subunit have demonstrated that partial deficiency of HIF-1 is sufficient to impair multiple physiological responses to continuous and intermittent hypoxia.

摘要

缺氧诱导因子1(HIF-1)是一种异源二聚体转录因子,由HIF-1α和HIF-1β亚基组成,作为氧稳态的主要调节因子发挥作用。HIF-1α的氧依赖性羟基化提供了一种机制,使氧合作用的变化能够传导至细胞核,从而导致基因表达的改变。缺氧诱导因子1在发育、生理和疾病发病机制中起关键作用。对编码HIF-1α亚基的基因座上等位基因无效的杂合小鼠的分析表明,HIF-1的部分缺陷足以损害对持续和间歇性缺氧的多种生理反应。

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