Document Detail

Defective release of Hepcidin not defective synthesis is the primary pathogenic mechanism in HFE-Haemochromatosis.
MedLine Citation:
PMID:  18054440     Owner:  NLM     Status:  MEDLINE    
Recent findings indicate a principal role for Hepcidin in iron homeostasis. Hepcidin is also thought to play a vital role in the pathogenic mechanism of anaemia in patients with inflammation or chronic disease. Under normal conditions influx and efflux of iron from duodenal enterocytes is regulated by Ferroportin. Ferroportin is a Hepcidin binding protein expressed in duodenal enterocytes. Hepcidin is a peptide synthesised in the liver and is the main regulator of iron homeostasis. It is a defensin like protein and exhibits anti-microbial and anti-fungal activity. The Hepcidin gene is principally expressed in hepatocytes but to a lesser extent in neutrophils and macrophages. Hereditary Haemochromatosis is caused by disruption of iron homeostasis due to mutations in the HFE gene (C282Y or H63D). Unrestricted uptake of iron by duodenal enterocytes causes iron overload which is the hallmark of the disease. Current thinking is that defective Hepcidin synthesis or defective iron-sensing mechanisms leading to Hepcidin deficiency is the cause of iron overload in HFE-Haemochromatosis. Thus HFE-Haemochromatosis has been described as an endocrine disease. Basal levels of Hepcidin appear to be normal in HFE-Haemochromatosis patients. This contradicts current theories of defective Hepcidin synthesis as the cause of Hereditary HFE-Haemochromatosis. We propose that the defect in HFE-Haemochromatosis is the loss of Hepcidin surge in response to intake of dietary iron and is not as a result of reduced synthesis.
Jayantha Arnold; Arvind Sangwaiya; Bharati Bhatkal; Ahran Arnold
Publication Detail:
Type:  Journal Article     Date:  2007-12-03
Journal Detail:
Title:  Medical hypotheses     Volume:  70     ISSN:  0306-9877     ISO Abbreviation:  Med. Hypotheses     Publication Date:  2008  
Date Detail:
Created Date:  2008-05-06     Completed Date:  2008-08-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7505668     Medline TA:  Med Hypotheses     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  1197-200     Citation Subset:  IM    
Department of Gastroenterology, Ealing Hospital NHS Trust, Uxbridge Road, Southall, Middlesex, UB1 3HW, United Kingdom. <>
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MeSH Terms
Anti-Bacterial Agents / metabolism*
Antimicrobial Cationic Peptides / secretion*
Hemochromatosis / etiology*,  genetics,  metabolism,  pathology
Histocompatibility Antigens Class I / genetics*
Iron Overload / metabolism
Membrane Proteins / genetics*
Models, Biological*
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Antimicrobial Cationic Peptides; 0/HFE protein, human; 0/Histocompatibility Antigens Class I; 0/Membrane Proteins; 0/hepcidin

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

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