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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2564-2570. Prepublished online as a Blood First Edition Paper on November 4, 2004; DOI 10.1182/blood-2004-03-1204. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-1204v1 105/6/2564    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Carlson, H. Articles by Enns, C. A. Search for Related Content PubMed PubMed Citation Articles by Carlson, H. Articles by Enns, C. A. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS The hereditary hemochromatosis protein, HFE, lowers intracellular iron levels independently of transferrin receptor 1 in TRVb cells Hanqian Carlson, An-Sheng Zhang, William H. Fleming, and Caroline A. Enns From the Department of Cell and Developmental Biology L215, Oregon Health & Science University, Portland, and the Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland. Hereditary hemochromatosis (HH) is an autosomal recessive disease that leads to parenchymal iron accumulation. The most common form of HH is caused by a single amino acid substitution in the HH protein, HFE, but the mechanism by which HFE regulates iron homeostasis is not known. In the absence of transferrin (Tf), HFE interacts with transferrin receptor 1 (TfR1) and the 2 proteins co-internalize, and in vitro studies have shown that HFE and Tf compete for TfR1 binding. Using a cell line lacking endogenous transferrin receptors (TRVb cells) transfected with different forms of HFE and TfR1, we demonstrate that even at low concentrations Tf competes effectively with HFE for binding to TfR1 on living cells. Transfection of TRVb cells or the derivative line TRVb1 (which stably expresses human TfR1) with HFE resulted in lower ferritin levels and decreased Fe2+ uptake. These data indicate that HFE can regulate intracellular iron storage independently of its interaction with TfR1. Earlier studies found that in HeLa cells, HFE expression lowers Tf-mediated iron uptake; here we show that HFE lowers non–Tf-bound iron in TRVb cells and add to a growing body of evidence that HFE may play different roles in different cell types. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Chen, M. Chloupkova, J. Gao, T. L. Chapman-Arvedson, and C. A. Enns HFE Modulates Transferrin Receptor 2 Levels in Hepatoma Cells via Interactions That Differ from Transferrin Receptor 1-HFE Interactions J. Biol. Chem., December 21, 2007; 282(51): 36862 - 36870. [Abstract] [Full Text] [PDF] A Pietrangelo Molecular insights into the pathogenesis of hereditary haemochromatosis. Gut, April 1, 2006; 55(4): 564 - 568. [Full Text] [PDF] A.-S. Zhang, A. P. West Jr., A. E. Wyman, P. J. Bjorkman, and C. A. Enns Interaction of Hemojuvelin with Neogenin Results in Iron Accumulation in Human Embryonic Kidney 293 Cells J. Biol. Chem., October 7, 2005; 280(40): 33885 - 33894. [Abstract] [Full Text] [PDF]

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