Document Detail


Prohepcidin binds to the HAMP promoter and autoregulates its own expression.
MedLine Citation:
PMID:  23390933     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepcidin is the major regulatory peptide hormone of iron metabolism, encoded by the HAMP (hepcidin antimicrobial peptide) gene. Hepcidin is expressed mainly in hepatocytes, but is also found in the blood in both a mature and prohormone form. Although, the function of mature hepcidin and the regulation of the HAMP gene have been extensively studied, the intracellular localization and the fate of prohepcidin remains controversial. In the present study, we propose a novel role for prohepcidin in the regulation of its own transcription. Using indirect immunofluorescence and mCherry tagging, a portion of prohepcidin was detected in the nucleus of hepatocytes. Prohepcidin was found to specifically bind to the STAT3 (signal transducer and activator of transcription 3) site in the promoter of HAMP. Overexpression of prohepcidin in WRL68 cells decreased HAMP promoter activity, whereas decreasing the amount of prohepcidin caused increased promoter activity measured by a luciferase reporter-gene assay. Moreover, overexpression of the known prohepcidin-binding partner, α-1 antitrypsin caused increased HAMP promoter activity, suggesting that only the non-α-1 antitrypsin-bound prohepcidin affects the expression of its own gene. The results of the present study indicate that prohepcidin can bind to and transcriptionally regulate the expression of HAMP, suggesting a novel autoregulatory pathway of hepcidin gene expression in hepatocytes.
Authors:
Edina Pandur; Katalin Sipos; László Grama; Judit Nagy; Viktor S Poór; György Sétáló; Attila Miseta; Zsuzsanna Fekete
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  451     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-28     Completed Date:  2013-05-29     Revised Date:  2013-07-05    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  301-11     Citation Subset:  IM    
Affiliation:
Department of Forensic Medicine, University of Pécs, Szigeti str 12, H-7624 Pécs, Hungary.
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MeSH Terms
Descriptor/Qualifier:
Antimicrobial Cationic Peptides / genetics*,  metabolism*
Binding Sites
Cell Line
Cell Nucleus / metabolism
Cytoplasm / metabolism
Down-Regulation
Gene Expression Regulation*
Hepatocytes / cytology,  metabolism
Humans
Promoter Regions, Genetic
Protein Precursors / genetics,  metabolism*
STAT3 Transcription Factor / metabolism
alpha 1-Antitrypsin / metabolism
Chemical
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/Protein Precursors; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/alpha 1-Antitrypsin; 0/hepcidin; 0/prohepcidin
Comments/Corrections
Comment In:
Biochem J. 2013 Jun 1;452(2):e3-5   [PMID:  23662810 ]

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