Divalent metal-dependent regulation of hepcidin expression by MTF-1.
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.
Balesaria
Sara
S
Department of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom. sara@biochem.ucl.ac.uk
Ramesh
Bala
B
McArdle
Harry
H
Bayele
Henry K
HK
Srai
Surjit K S
SK
D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002413:Cations, Divalent / Q000494:pharmacology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D064451:Hepcidins; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008670:Metals / Q000494:pharmacology*; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D015032:Zinc / Q000494:pharmacology; D000097809:Transcription Factor MTF-1
D023181:Antimicrobial Cationic Peptides; D002413:Cations, Divalent; D004268:DNA-Binding Proteins; D064451:Hepcidins; D008156:Luciferases; D008670:Metals; D014157:Transcription Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1; C578702:HAMP protein, human