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Mechanism of increased iron absorption in murine model of hereditary hemochromatosis: Increased duodenal expression of the iron transporter DMT1

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Fleming, Robert E., Migas, Mary C., Zhou, XiaoYan, Jiang, Jinxing, Britton, Robert S., Brunt, Elizabeth M., Tomatsu, Shunji, Waheed, Abdul, Bacon, Bruce R., Sly, William S.·1999·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.96.6.3143PMC PMC15909

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Abstract

Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by tissue iron deposition secondary to excessive dietary iron absorption. We recently reported that HFE, the protein defective in HH, was physically associated with the transferrin receptor (TfR) in duodenal crypt cells and proposed that mutations in HFE attenuate the uptake of transferrin-bound iron from plasma by duodenal crypt cells, leading to up-regulation of transporters for dietary iron. Here, we tested the hypothesis that HFE −/− mice have increased duodenal expression of the divalent metal transporter (DMT1). By 4 weeks of age, the HFE −/− mice demonstrated iron loading when compared with HFE +/+ littermates, with elevated transferrin saturations (68.4% vs. 49.8%) and elevated liver iron concentrations (985 μg/g vs. 381 μg/g). By using Northern blot analyses, we quantitated duodenal expression of both classes of DMT1 transcripts: one containing an iron responsive element (IRE), called DMT1(IRE), and one containing no IRE, called DMT1(non-IRE). The positive control for DMT1 up-regulation was a murine model of dietary iron deficiency that demonstrated greatly increased levels of duodenal DMT1(IRE) mRNA. HFE −/− mice also demonstrated an increase in duodenal DMT1(IRE) mRNA (average 7.7-fold), despite their elevated transferrin saturation and hepatic iron content. Duodenal expression of DMT1(non-IRE) was not increased, nor was hepatic expression of DMT1 increased. These data support the model for HH in which HFE mutations lead to inappropriately low crypt cell iron, with resultant stabilization of DMT1(IRE) mRNA, up-regulation of DMT1, and increased absorption of dietary iron.

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A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis
Feder, J. N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D. A., Basava, A., Dormishian, F., Domingo, R., Ellis, M. C., Fullan, A., et al. (1996) · Nature Genetics · doi:10.1038/ng0896-399 · Cited by 3,664
Self-citation
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Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., & Hediger, M. A. (1997) · Nature · doi:10.1038/41343 · Cited by 3,166
Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family
Fort, P., Marty, L., Piechaczyk, M., Sabrouty, S. R.-E., Dani, C., Jeanteur, P., & Blanchard, J. (1985) · Nucleic Acids Research · doi:10.1093/nar/13.5.1431 · Cited by 2,072
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Fleming, M. D., Romano, M. A., Su, M. A., Garrick, L. M., Garrick, M. D., & Andrews, N. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.3.1148 · Cited by 936
The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding
Feder, J. N., Penny, D. M., Irrinki, A., Lee, V. K., Lebrón, J. A., Watson, N., Tsuchihashi, Z., Sigal, E., Bjorkman, P. J., & Schatzman, R. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.4.1472 · Cited by 827
Crystal Structure of the Hemochromatosis Protein HFE and Characterization of Its Interaction with Transferrin Receptor
Lebrón, J. A., Bennett, M. J., Vaughn, D. E., Chirino, A. J., Snow, P. M., Mintier, G. A., Feder, J. N., & Björkman, P. J. (1998) · Cell · doi:10.1016/s0092-8674(00)81151-4 · Cited by 639
Prevalence of Hemochromatosis among 11,065 Presumably Healthy Blood Donors
Edwards, C. Q., Griffen, L. M., Goldgar, D. E., Drummond, C., Skolnick, M. H., & Kushner, J. P. (1988) · New England Journal of Medicine · doi:10.1056/nejm198805263182103 · Cited by 628
HFE gene knockout produces mouse model of hereditary hemochromatosis
Zhou, X. Y., Tomatsu, S., Fleming, R. E., Parkkila, S., Waheed, A., Jiang, J., Fei, Y., Brunt, E. M., Ruddy, D. A., Prass, C. E., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2492 · Cited by 519
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Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis
Parkkila, S., Waheed, A., Britton, R. S., Bacon, B. R., Zhou, X. Y., Tomatsu, S., Fleming, R. E., & Sly, W. S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.13198 · Cited by 336
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Lee, P. L., Gelbart, T., West, C., Halloran, C., & Beutler, E. (1998) · Blood Cells Molecules and Diseases · doi:10.1006/bcmd.1998.0186 · Cited by 318

Flagged first, then by citations

Show all 46 references

Research works printed but not linked: 7

P M Smith, B E Godfrey, R Williams Clin Sci 37, 519–531 (1969).
G D McLaren, M H Nathanson, A Jacobs, D Trevett, W Thomson J Lab Clin Med 117, 390–401 (1991).
J D Torrance, T H Bothwell Methods Haematol 1, 90–115 (1980).
J Fielding Methods Haematol 1, 15–43 (1980).
P R Flanagan, A Hajdu, P C Adams Hepatology 22, 828–832 (1995).
J C Barton, M A Patton, C Q Edwards, L M Griffen, J P Kushner, R G Meeks, R W Leggett J Lab Clin Med 124, 193–198 (1994).
Saarnio J. Parkkila S. Parkkila A.-K. Waheed A. Karttunen T. & Sly W. S. (1999) J. Histochem. Cytochem . in press.

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Expression of the DMT1 (NRAMP2/DCT1) iron transporter in mice with genetic iron overload disorders
Canonne‐Hergaux, F., Levy, J. E., Fleming, M. D., Montross, L. K., Andrews, N. C., & Gros, P. (2001) · Blood · doi:10.1182/blood.v97.4.1138 · Cited by 91
Tumor Necrosis Factor-α–Induced Iron Sequestration and Oxidative Stress in Human Endothelial Cells
Nanami, M., Ookawara, T., Otaki, Y., Ito, K., Moriguchi, R., Miyagawa, K., Hasuike, Y., Izumi, M., Eguchi, H., Suzuki, K., et al. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000190610.63878.20 · Cited by 87
Copper exposure modifies the content and distribution of trace metals in mammalian cultured cells
Tapia, L., Suazo, M., Christian Hodar, Q., Cambiazo, V., & González, M. (2003) · BioMetals · doi:10.1023/a:1020766932605 · Cited by 85
Molecular Mechanisms and Regulation of Iron Transport
Chung, J., & Wessling‐Resnick, M. (2003) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/713609332 · Cited by 86
Iron Transport
Wessling‐Resnick, M. (2000) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.20.1.129 · Cited by 83
Intestinal expression of genes involved in iron absorption in humans
Rolfs, A., Bonkovsky, H. L., Kohlroser, J. G., McNeal, K., Sharma, A. K., Berger, U. V., & Hediger, M. A. (2002) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00371.2001 · Cited by 82
Molecular aspects of iron absorption and HFE expression
Parkkila, S., Niemelä, O. J., Britton, R. S., Fleming, R. E., Waheed, A., Bacon, B. R., & Sly, W. S. (2001) · Gastroenterology · doi:10.1053/gast.2001.29617 · Cited by 79
Self-citation
Role of HFE in iron metabolism, hereditary haemochromatosis, anaemia of chronic disease, and secondary iron overload
Townsend, A., & Drakesmith, H. (2002) · The Lancet · doi:10.1016/s0140-6736(02)07885-6 · Cited by 79
Both the Environment and Genes Are Important for Concentrations of Cadmium and Lead in Blood
Bjorkman, L. L., Vahter, M., & Pedersen, N. L. (2000) · Environmental Health Perspectives · doi:10.1289/ehp.00108719 · Cited by 75
Physiologic systemic iron metabolism in mice deficient for duodenal Hfe
Spasić, M. V., Kiss, J., Herrmann, T. R. W., Kessler, R., Stolte, J., Galy, B., Rathkolb, B., Wolf, E., Stremmel, W., Hentze, M. W., et al. (2007) · Blood · doi:10.1182/blood-2006-07-036186 · Cited by 77
Iron transporter Nramp2/DMT-1 is associated with the membrane of phagosomes in macrophages and Sertoli cells
Jabado, N., Canonne‐Hergaux, F., Gruenheid, S., Picard, V., & Gros, P. (2002) · Blood · doi:10.1182/blood-2002-04-1182 · Cited by 75
Functional role of DMT1 in transferrin-independent iron uptake by human hepatocyte and hepatocellular carcinoma cell, HLF
SHINDO, M., Torimoto, Y., SAITO, H., Motomura, W., Ikuta, K., SATO, K., FUJIMOTO, Y., & KOHGO, Y. (2006) · Hepatology Research · doi:10.1016/j.hepres.2006.03.011 · Cited by 73
Biochemistry of Iron Uptake
Wessling‐Resnick, M. (1999) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409239991209318 · Cited by 73
Novel Roles for Iron Regulatory Proteins in the Adaptive Response to Iron Deficiency
Eisenstein, R. S., & Ross, K. L. (2003) · Journal of Nutrition · doi:10.1093/jn/133.5.1510s · Cited by 71
Iron transport: emerging roles in health and disease
Goswami, T., Rolfs, A., & Hediger, M. A. (2002) · Biochemistry and Cell Biology · doi:10.1139/o02-159 · Cited by 70
Both Nramp1 and DMT1 are necessary for efficient macrophage iron recycling
Soe-Lin, S., Apte, S. S., Mikhael, M. R., Kayembe, L. K., Nie, G., & Ponka, P. (2010) · Experimental Hematology · doi:10.1016/j.exphem.2010.04.003 · Cited by 69
Iron overload in adult Hfe-deficient mice independent of changes in the steady-state expression of the duodenal iron transporters DMT1 and Ireg1/ferroportin
Herrmann, T., Muckenthaler, M., van der Hoeven, F., Brennan, K., Gehrke, S. G., Hubert, N., Sergi, C., Gröne, H.-J., Kaiser, I., Gosch, I., et al. (2004) · Journal of Molecular Medicine · doi:10.1007/s00109-003-0508-x · Cited by 69
Increased hepcidin expression and hypoferraemia associated with an acute phase response are not affected by inactivation of HFE
Frazer, D. M., Wilkins, S. J., Millard, K. N., McKie, A. T., Vulpe, C. D., & Anderson, G. J. (2004) · British Journal of Haematology · doi:10.1111/j.1365-2141.2004.05044.x · Cited by 69
Detection of a [3Fe-4S] Cluster Intermediate of Cytosolic Aconitase in Yeast Expressing Iron Regulatory Protein 1
Brown, N. M., Kennedy, M. C., Antholine, W. E., Eisenstein, R. S., & Walden, W. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110282200 · Cited by 67
Clinical, biochemical and molecular findings in a series of families with hereditary hyperferritinaemia–cataract syndrome
Girelli, D., Bozzini, C., Zecchina, G., Tinazzi, E., Bosio, S., Piperno, A., Ramenghi, U., Peters, J., Levi, S., Camaschella, C., et al. (2001) · British Journal of Haematology · doi:10.1046/j.1365-2141.2001.03116.x · Cited by 69
Human Cytomegalovirus Protein US2 Interferes with the Expression of Human HFE, a Nonclassical Class I Major Histocompatibility Complex Molecule That Regulates Iron Homeostasis
Arieh, S. V.-B., Zimerman, B., Smorodinsky, N. I., Yaacubovicz, M., Schechter, C., Bačík, I., Gibbs, J., Bennink, J. R., Yewdell, J. W., Coligan, J. E., et al. (2001) · Journal of Virology · doi:10.1128/jvi.75.21.10557-10562.2001 · Cited by 66
Pathophysiology of Hereditary Hemochromatosis
Fleming, R. E., Britton, R. S., Waheed, A., Sly, W. S., & Bacon, B. R. (2005) · Seminars in Liver Disease · doi:10.1055/s-2005-923313 · Cited by 68
Self-citation
Hereditary hemochromatosis: update for 2003
Harrison, S. A., & Bacon, B. R. (2003) · Journal of Hepatology · doi:10.1016/s0168-8278(02)00428-2 · Cited by 64
Self-citation
Relation of hemochromatosis with hepatocellular carcinoma: epidemiology, natural history, pathophysiology, screening, treatment, and prevention
Harrison, S. A., & Bacon, B. R. (2005) · Medical Clinics of North America · doi:10.1016/j.mcna.2004.08.005 · Cited by 62
Self-citation
Duodenal expression of iron transport molecules in untreated haemochromatosis subjects
Stuart, K. A., Anderson, G. J., Frazer, D. M., Powell, L. W., McCullen, M., Fletcher, L. M., & Crawford, D. H. G. (2003) · Gut · doi:10.1136/gut.52.7.953 · Cited by 61
Functional and molecular responses of human intestinal Caco-2 cells to iron treatment
Tallkvist, J., Bowlus, C. L., & Lönnerdal, B. L. (2000) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/72.3.770 · Cited by 62
Intestinal iron uptake determined by divalent metal transporter is enhanced in HFE-deficient mice with hemochromatosis
Griffiths, W. J., Cox, T. M., & Sly, W. S. (2001) · Gastroenterology · doi:10.1053/gast.2001.24050 · Cited by 61
Self-citation
Duodenal cytochrome B and hephaestin expression in patients with iron deficiency and hemochromatosis
Zoller, H., Theurl, I., Koch, R., McKie, A. T., Vogel, W., & Weiss, G. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)01063-1 · Cited by 60

Authors: Fleming, R. E., Migas, M. C., Zhou, X., Jiang, J., Britton, R. S., Brunt, E. M., Tomatsu, S., Waheed, A., Bacon, B. R., & Sly, W. S.
Affiliations: Saint Louis University (US)
Department of Pediatrics, Edward A. Doisy Department of Biochemistry and Molecular Biology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, and Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO 63104
ORCID: Fleming, Robert E.
Brunt, Elizabeth M.
Tomatsu, Shunji
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1999-03-16
Volume: 96
Issue: 6
Pages: 3143-3148
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.96.6.3143
PMC: PMC15909
OpenAlex: W2089161230
Cited by: 269
References: 46
Citations by year: 2026: 1 · 2025: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 7 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 7 · 2014: 7 · 2013: 5 · 2012: 5
FWCI: 21.44
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (GM34182)
National Institute of General Medical Sciences (GM35182, R01GM034182)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 53405, R01DK041816, DK 41816, R01DK053405)
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords: hereditary hemochromatosis, HFE gene, DMT1, iron absorption, iron-responsive element, transferrin receptor, dietary iron deficiency, iron overload, liver iron concentration, transferrin saturation, Hfe knockout mice
MeSH terms: Solute Carrier Family 11, Member 2, Animals, Carrier Proteins, Duodenum, Hemochromatosis, Iron, Mutation, Cation Transport Proteins, Iron-Binding Proteins, Mice

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Mechanism of increased iron absorption in murine model of hereditary hemochromatosis: Increased duodenal expression of the iron transporter DMT1

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