Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: Evidence for an alcohol-induced hypoxic response

Heritage, Mandy L., Murphy, Therese L., Bridle, Kim R., Anderson, Gregory J., Crawford, Darrell H. G. and Fletcher, Linda M. (2009) Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: Evidence for an alcohol-induced hypoxic response. Alcoholism, Clinical and Experimental Research, 33 8: 1391-1400. doi:10.1111/j.1530-0277.2009.00969.x


Author Heritage, Mandy L.
Murphy, Therese L.
Bridle, Kim R.
Anderson, Gregory J.
Crawford, Darrell H. G.
Fletcher, Linda M.
Title Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: Evidence for an alcohol-induced hypoxic response
Journal name Alcoholism, Clinical and Experimental Research   Check publisher's open access policy
ISSN 0145-6008
1530-0277
Publication date 2009-01-01
Year available 2009
Sub-type Article (original research)
DOI 10.1111/j.1530-0277.2009.00969.x
Open Access Status DOI
Volume 33
Issue 8
Start page 1391
End page 1400
Total pages 10
Editor Harriet de Wit
Ivan Diamond
Place of publication Maryland, U.S.A.
Publisher Blackwell
Language eng
Subject 110307 Gastroenterology and Hepatology
C1
920105 Digestive System Disorders
Abstract Background/Aims: Expression of Hamp1, the gene encoding the iron regulatory peptide hepcidin, is inappropriately low in HFE-associated hereditary hemochromatosis and Hfe knockout mice (Hfe(-/-)). Since chronic alcohol consumption is also associated with disturbances in iron metabolism, we investigated the effects of alcohol consumption on hepcidin mRNA expression in Hfe(-/-) mice.
Formatted abstract
Background /Aims:
Expression of Hamp1, the gene encoding the iron regulatory peptide hepcidin, is inappropriately low in HFE-associated hereditary hemochromatosis and Hfe knockout mice (Hfe−/−). Since chronic alcohol consumption is also associated with disturbances in iron metabolism, we investigated the effects of alcohol consumption on hepcidin mRNA expression in Hfe−/− mice.

Methods:
Hfe −/− and C57BL/6 (wild-type) mice were pair-fed either an alcohol liquid diet or control diet for up to 8 weeks. The mRNA levels of hepcidin and ferroportin were measured at the mRNA level by RT-PCR and protein expression of hypoxia inducible factor-1 alpha (HIF-1α) was measured by western blot.

Results:
Hamp1 mRNA expression was significantly decreased and duodenal ferroportin expression was increased in alcohol-fed wild-type mice at 8 weeks. Time course experiments showed that the decrease in hepcidin mRNA was not immediate, but was significant by 4 weeks. Consistent with the genetic defect, Hamp1 mRNA was decreased and duodenal ferroportin mRNA expression was increased in Hfe−/− mice fed on the control diet compared with wild-type animals and alcohol further exacerbated these effects. HIF-1α protein levels were elevated in alcohol-fed wild-type animals compared with controls.

Conclusion:
Alcohol may decrease Hamp1 gene expression independently of the HFE pathway possibly via alcohol-induced hypoxia.
Keyword Iron Regulation
Iron-metabolism
Hemochromatosis
Cofactors
Liver Disease
HIF-1α
STAT3
CEBP α
Ferroportin
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Thu, 03 Sep 2009, 17:49:03 EST by Mr Andrew Martlew on behalf of Medicine - Princess Alexandra Hospital