Expression of hypoxia-inducible factor 1: Mechanisms and consequences
Expression of hypoxia-inducible factor 1: Mechanisms and consequences
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DOI：
10.1016/s0006-2952(99)00292-0
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发表时间：
2000-01-01
影响因子：
5.8
通讯作者：
Semenza, GL
中科院分区：
文献类型：
--
作者：
Semenza, GL
缺氧诱导因子1（Hypoxia-inducible factor 1，HIF-1）是一种基本的螺旋环螺旋结构的转录因子，在哺乳动物的发育和生理过程中起重要作用。HIF-1是由HIF-1 α和HIF-1 β亚基组成的异源二聚体。HIF-1 α亚基的表达和活性受到细胞内O-2浓度的严格调节。在缺氧条件下，HIF-1激活编码促红细胞生成素、葡萄糖转运蛋白、糖酵解酶、血管内皮生长因子的基因以及其蛋白质产物增加O-2递送或促进对缺氧的代谢适应的其他基因的转录。HIF-1对于胚胎血管形成和存活、缺血心肌中的新血管形成、缺氧诱导的肺血管重塑和肿瘤血管形成至关重要。由于瘤内缺氧的存在以及编码癌蛋白和肿瘤抑制因子的基因突变，HIF-1 α在大多数常见人类癌症及其转移灶中过表达。HIF-1水平的药理学操作可能为代表西方社会最常见死亡原因的疾病提供新的治疗方法，包括癌症，慢性肺病和心肌缺血。生物化学制药59;1：47-53，2000. (C)1999 Elsevier Science Inc.
Hypoxia-inducible factor 1 (HIF-1) is a basic-helix-loop-helix transcription factor that plays essential roles in mammalian development and physiology. HIF-1 is a heterodimer composed of HIF-1 alpha and HIF-1 beta subunits. The expression and activity of the HIF-1 alpha subunit are tightly regulated by cellular O-2 concentration. Under hypoxic conditions, HIF-1 activates the transcription of genes encoding erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, and other genes whose protein products increase O-2 delivery or facilitate metabolic adaptation to hypoxia. HIF-1 is essential for embryonic vascularization and survival, neovascularization in ischemic myocardium, hypoxia-induced pulmonary vascular remodeling, and tumor vascularization. HIF-1 alpha is overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors. Pharmacologic manipulation of HIF-1 levels may provide a novel therapeutic approach to diseases that represent the most common causes of mortality in Western society, including cancer, chronic lung disease, and myocardial ischemia. BIOCHEM PHARMACOL 59;1:47-53, 2000. (C) 1999 Elsevier Science Inc.