Limited iron export by hepatocytes contributes to hepatic iron-loading in the Hfe knockout mouse

A.C.G. Chua; S.F. Drake; C.E. Herbison; J.K. Olynyk; P.J. Leedman; D. Trinder

doi:10.1016/j.jhep.2005.08.012

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Limited iron export by hepatocytes contributes to hepatic iron-loading in the Hfe knockout mouse

Journal article

Peer reviewed

Limited iron export by hepatocytes contributes to hepatic iron-loading in the Hfe knockout mouse

A.C.G. Chua, S.F. Drake, C.E. Herbison, J.K. Olynyk, P.J. Leedman and D. Trinder

Journal of Hepatology, Vol.44(1), pp.176-182

2006

DOI: https://doi.org/10.1016/j.jhep.2005.08.012

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Abstract

Background/Aims In hereditary hemochromatosis, iron-loading of hepatocytes is associated with increased iron uptake while little is known about iron release. This study aims to characterise iron release and ferroportin expression by Hfe knockout hepatocytes to determine if they contribute to iron overload in haemochromatosis. Methods Iron release by hepatocytes from Hfe knockout, non-iron-loaded and iron-loaded wild-type mice was measured after incubation with nontransferrin-bound iron as iron-citrate. Results Iron release and ferroportin expression by hepatocytes from Hfe knockout, non-iron-loaded and in vivo iron-loaded wild-type mice were similar although, nontransferrin-bound iron uptake was significantly increased in Hfe knockout hepatocytes and decreased in iron-loaded wild-type hepatocytes compared with non-iron-loaded wild-type cells. When expressed as a percentage of total iron uptake, iron release was decreased in Hfe knockout hepatocytes (4.6±0.7 versus 13.7±1.2%, P<0.0001) and increased in iron-loaded wild-type hepatocytes (29.5±0.5 versus 13.5±0.7%; P<0.0001) compared with wild-type hepatocytes. In contrast, in vitro iron-loading increased iron release and ferroportin expression by both Hfe knockout and wild-type hepatocytes. Conclusions Hfe knockout hepatocytes accumulate iron as a result of limited iron export and enhanced iron uptake. The correlation between iron release and ferroportin expression suggests that iron export in hepatocytes is mediated by ferroportin.

Details

Title: Limited iron export by hepatocytes contributes to hepatic iron-loading in the Hfe knockout mouse
Authors/Creators: A.C.G. Chua (Author/Creator) - Fremantle Hospital
S.F. Drake (Author/Creator) - Fremantle Hospital
C.E. Herbison (Author/Creator) - Fremantle Hospital
J.K. Olynyk (Author/Creator) - Western Australian Institute for Medical Research, Nedlands, WA 6009, Australia
P.J. Leedman (Author/Creator) - Royal Perth Hospital
D. Trinder (Author/Creator) - Western Australian Institute for Medical Research, Nedlands, WA 6009, Australia
Publication Details: Journal of Hepatology, Vol.44(1), pp.176-182
Publisher: Elsevier
Identifiers: 991005540258407891
Copyright: 2005 European Association for the Study of the Liver
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.184 Physiology & Metals; 1.184.573 Iron Metabolism
Web Of Science research areas: Gastroenterology & Hepatology
ESI research areas: Clinical Medicine