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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1509-1514. Prepublished online as a Blood First Edition Paper on October 16, 2003; DOI 10.1182/blood-2003-07-2378. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2378v1 103/4/1509    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 Zhang, A.-S. Articles by Enns, C. A. Search for Related Content PubMed PubMed Citation Articles by Zhang, A.-S. Articles by Enns, C. A. Related Collections Red Cells Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Localization of iron metabolism–related mRNAs in rat liver indicate that HFE is expressed predominantly in hepatocytes An-Sheng Zhang, Shigang Xiong, Hidekazu Tsukamoto, and Caroline A. Enns From the Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR; Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA; and Department of Veterans Affairs, Greater Los Angeles Healthcare Systems, Los Angeles, CA. The mRNAs of proteins involved in iron metabolism were measured in isolated hepatocytes, Kupffer cells, sinusoidal endothelial cells (SECs), and hepatic stellate cells (HSCs). Levels of type I hereditary hemochromatosis gene (HFE), transferrin, hepcidin, transferrin receptors 1 and 2 (TfR1, TfR2), ferroportin 1 (FPN1), divalent metal transporter 1 (DMT1), natural resistance–associated macrophage protein 1 (Nramp1), ceruloplasmin, hephaestin, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), were measured by quantitative reverse-transriptase polyerase chain reaction (qRT-PCR). We show that hepatocytes express almost all the iron-related genes tested, in keeping with their central role in iron metabolism. In addition, hepatocytes had 10-fold lower TfR1 mRNA levels than TfR2 and the lowest levels of TfR1 of the 4 cell types isolated. Kupffer cells, which process senescent red blood cells and recycle the iron, had high levels of ferroportin 1, ceruloplasmin, and hephaestin mRNA. Most important, of all the cell types tested, hepatocytes had the highest level of HFE mRNA, a factor of 10 higher than Kupffer cells. In situ hybridization analysis was conducted with rat liver sections. Consistent with the qRT-PCR analysis, HFE gene expression was localized mainly in hepatocytes. Western blot analysis confirmed this finding. Unexpectedly, HSCs also had high levels of DMT1 and ferroportin, implicating them in either iron sensing or iron cycling. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: HFE, a putative hepatocyte iron sensor? Surjit K. S. Srai Blood 2004 103: 1177. [Full Text] [PDF] This article has been cited by other articles: A.-S. Zhang, F. Yang, K. Meyer, C. Hernandez, T. Chapman-Arvedson, P. J. Bjorkman, and C. A. Enns Neogenin-mediated Hemojuvelin Shedding Occurs after Hemojuvelin Traffics to the Plasma Membrane J. Biol. Chem., June 20, 2008; 283(25): 17494 - 17502. [Abstract] [Full Text] [PDF] 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.-S. Zhang, S. A. Anderson, K. R. Meyers, C. Hernandez, R. S. Eisenstein, and C. A. Enns Evidence That Inhibition of Hemojuvelin Shedding in Response to Iron Is Mediated through Neogenin J. Biol. Chem., April 27, 2007; 282(17): 12547 - 12556. [Abstract] [Full Text] [PDF] M. B. Johnson, J. Chen, N. Murchison, F. A. Green, and C. A. Enns Transferrin Receptor 2: Evidence for Ligand-induced Stabilization and Redirection to a Recycling Pathway Mol. Biol. Cell, March 1, 2007; 18(3): 743 - 754. [Abstract] [Full Text] [PDF] K. Thompson, R. M. Molina, J. D. Brain, and M. Wessling-Resnick Belgrade Rats Display Liver Iron Loading J. Nutr., December 1, 2006; 136(12): 3010 - 3014. [Abstract] [Full Text] [PDF] K. B Hadley, L. K Johnson, and J. R Hunt Iron absorption by healthy women is not associated with either serum or urinary prohepcidin Am. J. Clinical Nutrition, July 1, 2006; 84(1): 150 - 155. [Abstract] [Full Text] [PDF] A. Donovan, C. N. Roy, and N. C. Andrews The Ins and Outs of Iron Homeostasis Physiology, April 1, 2006; 21(2): 115 - 123. [Abstract] [Full Text] [PDF] R. E. Fleming and R. S. Britton Iron Imports. VI. HFE and regulation of intestinal iron absorption Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G590 - G594. [Abstract] [Full Text] [PDF] J. Chen, D. A. Rider, and R. Ruan Identification of Valid Housekeeping Genes and Antioxidant Enzyme Gene Expression Change in the Aging Rat Liver J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2006; 61(1): 20 - 27. [Abstract] [Full Text] [PDF] C. Camaschella Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders Blood, December 1, 2005; 106(12): 3710 - 3717. [Abstract] [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] D. M. Frazer and G. J. Anderson Iron Imports. I. Intestinal iron absorption and its regulation Am J Physiol Gastrointest Liver Physiol, October 1, 2005; 289(4): G631 - G635. [Abstract] [Full Text] [PDF] H. Makui, R. J. Soares, W. Jiang, M. Constante, and M. M. Santos Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading Blood, September 15, 2005; 106(6): 2189 - 2195. [Abstract] [Full Text] [PDF] L. Viatte, J.-C. Lesbordes-Brion, D.-Q. Lou, M. Bennoun, G. Nicolas, A. Kahn, F. Canonne-Hergaux, and S. Vaulont Deregulation of proteins involved in iron metabolism in hepcidin-deficient mice Blood, June 15, 2005; 105(12): 4861 - 4864. [Abstract] [Full Text] [PDF] H. Carlson, A.-S. Zhang, W. H. Fleming, and C. A. Enns The hereditary hemochromatosis protein, HFE, lowers intracellular iron levels independently of transferrin receptor 1 in TRVb cells Blood, March 15, 2005; 105(6): 2564 - 2570. [Abstract] [Full Text] [PDF] M. B. Johnson and C. A. Enns Diferric transferrin regulates transferrin receptor 2 protein stability Blood, December 15, 2004; 104(13): 4287 - 4293. [Abstract] [Full Text] [PDF] A. D. Robb, M. Ericsson, and M. Wessling-Resnick Transferrin receptor 2 mediates a biphasic pattern of transferrin uptake associated with ligand delivery to multivesicular bodies Am J Physiol Cell Physiol, December 1, 2004; 287(6): C1769 - C1775. [Abstract] [Full Text] [PDF] K J H Robson, A T Merryweather-Clarke, E Cadet, V Viprakasit, M G Zaahl, J J Pointon, D J Weatherall, and J Rochette Recent advances in understanding haemochromatosis: a transition state J. Med. Genet., October 1, 2004; 41(10): 721 - 730. [Abstract] [Full Text] [PDF] P. S. Davies and C. A. Enns Expression of the Hereditary Hemochromatosis Protein HFE Increases Ferritin Levels by Inhibiting Iron Export in HT29 Cells J. Biol. Chem., June 11, 2004; 279(24): 25085 - 25092. [Abstract] [Full Text] [PDF] C. J. Miranda, H. Makui, N. C. Andrews, and M. M. Santos Contributions of {beta}2-microglobulin-dependent molecules and lymphocytes to iron regulation: insights from HfeRag1-/- and {beta}2mRag1-/- double knock-out mice Blood, April 1, 2004; 103(7): 2847 - 2849. [Abstract] [Full Text] [PDF]

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