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低氧诱导因子对铁代谢的调节

许曼曼, 王俊, 谢俊霞^*

青岛大学医学院生理学教研室，山东省神经相关疾病重点实验室，山东省神经退变疾病协同创新中心，青岛 266071

摘要

低氧诱导因子(hypoxia-inducible factors, HIFs)是一类介导细胞内低氧反应的核转录复合体。HIF-α和HIF-β形成有功能的异质二聚体。哺乳动物中有HIF-1α、HIF-2α和HIF-3α。HIFs在铁代谢中发挥重要作用。受HIFs调节的铁代谢相关蛋白主要有二价金属转运蛋白1 (divalent metal transporter 1, DMT1)、铁转出蛋白(ferroportin 1, FPN1)、十二指肠铁细胞色素b (duodenal cytochrome b, Dcytb)和转铁蛋白受体(transferrin receptor, TfR)。铁调素(hepcidin)和铁调节蛋白(iron regulatory proteins, IRPs)是调节机体与细胞内铁代谢、维持铁稳态的重要因子，同样受到HIFs的调节。本文综述了HIFs对上述铁代谢相关蛋白的调节作用，以期为治疗铁代谢相关疾病提供可能的靶点。

关键词： 低氧诱导因子; 铁代谢 ; 二价金属转运蛋白1 ; 铁转出蛋白

分类号：Q4

Regulation of iron metabolism by hypoxia-inducible factors

XU Man-Man, Wang Jun, XIE Jun-Xia^*

Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Medical College of Qingdao University, Qingdao 266071, China

Abstract

Hypoxia-inducible factors (HIFs) are central mediators of cellular adaption to hypoxia. The heterodimeric HIF transcription factors consist of HIF-α and HIF-β, that form functional HIFs. Mammals contain HIF-1α, HIF-2α, and HIF-3α. HIFs play a key role in iron metabolism by regulating the expression of iron-related proteins, such as divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1), duodenal cytochrome b (Dcytb), and transferrin receptor (TfR). Hepcidin and iron regulatory proteins (IRPs), the central mediators for systematic and intracellular iron homeostasis, are also regulated by HIFs. In this review, we summarized the regulatory effects of HIFs on iron-related proteins, thus providing insights into the control of HIFs as therapeutic strategies for some iron related disorders.

Key words: hypoxia-inducible factors; iron metabolism ; divalent metal transporter 1 ; ferroportin 1

收稿日期：2017-04-25　　录用日期：2017-08-25

通讯作者：谢俊霞　　E-mail: jxiaxie@public.qd.sd.cn

DOI: 10.13294/j.aps.2017.0054

引用本文：

许曼曼, 王俊, 谢俊霞. 低氧诱导因子对铁代谢的调节[J]. 生理学报 2017; 69 (5): 598-610.

XU Man-Man, Wang Jun, XIE Jun-Xia. Regulation of iron metabolism by hypoxia-inducible factors . Acta Physiol Sin 2017; 69 (5): 598-610 (in Chinese with English abstract).