Journal article
The role of Hfe in transferrin-bound iron uptake by hepatocytes
Hepatology, Vol.47(5), pp.1737-1744
2008
Abstract
HFE-related hereditary hemochromatosis results in hepatic iron overload. Hepatocytes acquire transferrin-bound iron via transferrin receptor (Tfr) 1 and Tfr1-independent pathways (possibly Tfr2-mediated). In this study, the role of Hfe in the regulation of hepatic transferrin-bound iron uptake by these pathways was investigated using Hfe knockout mice. Iron and transferrin uptake by hepatocytes from Hfe knockout, non–iron-loaded and iron-loaded wild-type mice were measured after incubation with 50 nM 125I-Tf-59Fe (Tfr1 pathway) and 5 μM 125I-Tf-59Fe (Tfr1-independent or putative Tfr2 pathway). Tfr1 and Tfr2 messenger RNA (mRNA) and protein expression were measured by real-time polymerase chain reaction and western blotting, respectively. Tfr1-mediated iron and transferrin uptake by Hfe knockout hepatocytes were increased by 40% to 70% compared with iron-loaded wild-type hepatocytes with similar iron levels and Tfr1 expression. Iron and transferrin uptake by the Tfr1-independent pathway was approximately 100-fold greater than by the Tfr1 pathway and was not affected by the absence of Hfe. Diferric transferrin increased hepatocyte Tfr2 protein expression, resulting in a small increase in transferrin but not iron uptake by the Tfr1-independent pathway. Conclusion: Tfr1-mediated iron uptake is regulated by Hfe in hepatocytes. The Tfr1-independent pathway exhibited a much greater capacity for iron uptake than the Tfr1 pathway but it was not regulated by Hfe. Diferric transferrin up-regulated hepatocyte Tfr2 protein expression but not iron uptake, suggesting that Tfr2 may have a limited role in the Tfr1-independent pathway.
Details
- Title
- The role of Hfe in transferrin-bound iron uptake by hepatocytes
- Authors/Creators
- A.C.G. Chua (Author/Creator) - The University of Western AustraliaC.E. Herbison (Author/Creator) - The University of Western AustraliaS.F. Drake (Author/Creator) - The University of Western AustraliaR.M. Graham (Author/Creator) - The University of Western AustraliaJ.K. Olynyk (Author/Creator) - Western Australian Institute for Medical Research, Western Australia, AustraliaD. Trinder (Author/Creator) - Western Australian Institute for Medical Research, Western Australia, Australia
- Publication Details
- Hepatology, Vol.47(5), pp.1737-1744
- Publisher
- John Wiley & Sons Inc.
- Identifiers
- 991005541892907891
- Copyright
- © 2008 American Association for the Study of Liver Diseases
- 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