Effect of hypoxia on the expression of iron regulatory proteins 1 and the mechanisms involved.

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.

• Authors: Qian-Qian Luo, Dan Wang, Min-Yan Yu, Li Zhu
• Journal: IUBMB life (IUBMB Life) Vol. 63 Issue 2 Pg. 120-8 (Feb 2011) ISSN: 1521-6551 [Electronic] England
• PMID: 21360641 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley Periodicals, Inc.

Chemical References

• Hypoxia-Inducible Factor 1
• Iron
• Luciferases
• Iron Regulatory Protein 1
• Oxygen

Topics

• 5' Flanking Region
• Base Sequence
• Binding Sites (genetics)
• Cell Hypoxia (genetics)
• Down-Regulation
• Gene Expression Regulation
• Genes, Reporter
• Hep G2 Cells
• Humans
• Hypoxia (genetics, metabolism)
• Hypoxia-Inducible Factor 1 (genetics, metabolism)
• Iron (metabolism)
• Iron Regulatory Protein 1 (genetics, metabolism)
• Luciferases (metabolism)
• Molecular Sequence Data
• Oxygen (metabolism)
• Protein Binding (genetics)
• Response Elements (genetics)
• Up-Regulation