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Effect of hypoxia on the expression of iron regulatory proteins 1 and the mechanisms involved
Author(s) -
Luo QianQian,
Wang Dan,
Yu MinYan,
Zhu Li
Publication year - 2011
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.419
Subject(s) - hypoxia (environmental) , downregulation and upregulation , microbiology and biotechnology , hypoxia inducible factors , reporter gene , hypoxia inducible factor 1 , regulation of gene expression , gene expression , transfection , biology , chemistry , gene , oxygen , biochemistry , organic chemistry
Abstract Iron is essential for many biological processes, including oxygen delivery, and its supply is tightly regulated. Iron regulatory proteins (IRPs, IRP1 and IRP2) are master regulators of cellular iron metabolism. Hypoxia triggers a broad range of gene responses that are primarily mediated by hypoxia‐inducible factor‐1 (HIF‐1). In this study, we have shown that hypoxia could not only upregulate the expression of hypoxia inducible factor‐1 but also downregulate the expression of IRP1. However, the molecular mechanisms that govern the IRP1 response to hypoxia are not known. Herein we suggested that HIF/HRE system was an essential link between IRP1 and hypoxia. The HRE of IRP1 5′‐regulation regions could combine with HIF‐1 in vitro . Dual‐luciferase reporter assay showed that IRP1 was directly downregulated by HIF/HRE system. © 2011 IUBMB IUBMB Life, 63(2): 120–128, 2011