Document Detail


Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.
MedLine Citation:
PMID:  15514116     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepcidin is a peptide hormone secreted by the liver in response to iron loading and inflammation. Decreased hepcidin leads to tissue iron overload, whereas hepcidin overproduction leads to hypoferremia and the anemia of inflammation. Ferroportin is an iron exporter present on the surface of absorptive enterocytes, macrophages, hepatocytes, and placental cells. Here we report that hepcidin bound to ferroportin in tissue culture cells. After binding, ferroportin was internalized and degraded, leading to decreased export of cellular iron. The posttranslational regulation of ferroportin by hepcidin may thus complete a homeostatic loop: Iron regulates the secretion of hepcidin, which in turn controls the concentration of ferroportin on the cell surface.
Authors:
Elizabeta Nemeth; Marie S Tuttle; Julie Powelson; Michael B Vaughn; Adriana Donovan; Diane McVey Ward; Tomas Ganz; Jerry Kaplan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-10-28
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  306     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-12-17     Completed Date:  2005-01-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2090-3     Citation Subset:  IM    
Affiliation:
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antimicrobial Cationic Peptides / chemical synthesis,  genetics,  metabolism*,  pharmacology
Biological Transport
Cation Transport Proteins / metabolism*
Cell Line
Cell Membrane / metabolism
Cytosol / metabolism
Ferritins / metabolism
Hela Cells
Homeostasis
Humans
Iron / metabolism*
Iron Regulatory Protein 2 / metabolism
Lysosomes / metabolism
Mice
Protein Binding
RNA, Messenger / genetics,  metabolism
Receptor, Epidermal Growth Factor / metabolism
Recombinant Fusion Proteins / metabolism
Transfection
Transferrin / metabolism
Grant Support
ID/Acronym/Agency:
DK065029/DK/NIDDK NIH HHS; DK30534/DK/NIDDK NIH HHS; HL26922/HL/NHLBI NIH HHS; T35HL007744/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/Cation Transport Proteins; 0/RNA, Messenger; 0/Recombinant Fusion Proteins; 0/hepcidin; 0/metal transporting protein 1; 11096-37-0/Transferrin; 7439-89-6/Iron; 9007-73-2/Ferritins; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 4.2.1.3/Iron Regulatory Protein 2
Comments/Corrections
Comment In:
Science. 2004 Dec 17;306(5704):2051-3   [PMID:  15604397 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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