Abstract
Hepcidin is a small acute phase peptide that regulates iron absorption. It is induced by inflammation and infection, but is repressed by anaemia and hypoxia. Here we further reveal that hepcidin transcription also involves interactions between functional metal response elements (MREs) in its promoter, and the MRE-binding transcription factor-1. Analysis of hepcidin mRNA and protein levels in hepatoma cells suggests that its expression may be regulated by divalent metal ions, with zinc inducing maximal effects on hepcidin levels. These data suggest that this peptide may be a pleiotropic sensor of divalent metals, some of which are xenobiotic environmental toxins.
Copyright 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antimicrobial Cationic Peptides / genetics*
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Antimicrobial Cationic Peptides / metabolism
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Binding Sites / genetics
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Blotting, Western
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Cations, Divalent / pharmacology
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Cell Line, Tumor
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Electrophoretic Mobility Shift Assay
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Gene Expression Regulation / drug effects*
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Hepcidins
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Humans
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Luciferases / genetics
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Luciferases / metabolism
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Metals / pharmacology*
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Mutation
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Promoter Regions, Genetic / genetics
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Protein Binding
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Response Elements / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factor MTF-1
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic / drug effects
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Transfection
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Zinc / pharmacology
Substances
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Antimicrobial Cationic Peptides
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Cations, Divalent
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DNA-Binding Proteins
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HAMP protein, human
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Hepcidins
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Metals
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Transcription Factors
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Luciferases
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Zinc