ArticleProceedings of the National Academy of Sciences of the United States of America2002
Iron uptake from plasma transferrin by the duodenum is impaired in the Hfe knockout mouse.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 95 citations in OpenAlex.
- Mammary Leukocyte-Assisted Nanoparticle Transport Enhances Targeted Milk Trace Mineral Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Complex and Dynamic Interactions between Parvovirus Capsids, Transferrin Receptors, and Antibodies Control Cell Infection and Host Range.Journal of virology · 2018Article
- Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis.PloS one · 2018Article
- Gene co-expression networks shed light into diseases of brain iron accumulation.Neurobiology of disease · 2016Article
- Article
- Systems analysis of iron metabolism: the network of iron pools and fluxes.BMC systems biology · 2010Article
- Iron uptake from plasma transferrin by a transferrin receptor 2 mutant mouse model of haemochromatosis.Journal of hepatology · 2010Article
- Global transcriptional response to Hfe deficiency and dietary iron overload in mouse liver and duodenum.PloS one · 2009Article
- Function of the hemochromatosis protein HFE: Lessons from animal models.World journal of gastroenterology · 2008Article
- The relevance of the intestinal crypt and enterocyte in regulating iron absorption.Pflugers Archiv : European journal of physiology · 2007Review
- Normal iron metabolism and the pathophysiology of iron overload disorders.The Clinical biochemist. Reviews · 2006Article
- Pathophysiology of hereditary hemochromatosis.Seminars in liver disease · 2005Review
- The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation.Bone marrow transplantation · 2005Article
- Manipulation of iron to determine survival: competition between host and pathogen.Immunologic research · 2004Review
- Iron overload in adult Hfe-deficient mice independent of changes in the steady-state expression of the duodenal iron transporters DMT1 and Ireg1/ferroportin.Journal of molecular medicine (Berlin, Germany) · 2004Article
- Mechanisms of HFE-induced regulation of iron homeostasis: Insights from the W81A HFE mutation.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- The haemochromatosis protein HFE induces an apparent iron-deficient phenotype in H1299 cells that is not corrected by co-expression of beta 2-microglobulin.The Biochemical journal · 2003Article
- The hemochromatosis protein HFE inhibits iron export from macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- HFE and non-HFE hemochromatosis.International journal of hematology · 2002Review
- Molecular pathogenesis of iron overload.Gut · 2002Review
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Hereditary hemochromatosis (HH) is a disorder of iron metabolism in which enhanced iron absorption of dietary iron causes increased iron accumulation in the liver, heart, and pancreas. Most individuals with HH are homozygous for a C282Y mutation in the HFE gene. The function of HFE protein is unknown, but it is hypothesized that it acts in association with beta(2)-microglobulin and transferrin receptor 1 to regulate iron uptake from plasma transferrin by the duodenum, the proposed mechanism by which body iron levels are sensed. The aim of this study was to test this hypothesis by comparing clearance of transferrin-bound iron in Hfe knockout (KO) mice with that observed in C57BL/6 control mice. The mice were fed either an iron-deficient, control, or iron-loaded diet for 6 weeks to alter body iron status. The mice then were injected i.v. with (59)Fe-transferrin, and blood samples were taken over 2 h to determine the plasma (59)Fe turnover. After 2 h, the mice were killed and the amount of radioactivity in the duodenum, liver, and kidney was measured. In both Hfe KO and C57BL/6 mice, plasma iron turnover and iron uptake from plasma transferrin by the duodenum, liver, and kidney correlated positively with plasma iron concentration. However, duodenal iron uptake from plasma transferrin was decreased in the Hfe KO mice compared with the control mice. Despite this difference in duodenal uptake, the Hfe KO mice showed no decrease in iron uptake by the liver and kidney or alteration in the plasma iron turnover when compared with C57BL/6 mice. These data support the hypothesis that HFE regulates duodenal uptake of transferrin-bound iron from plasma, and that this mechanism of sensing body iron status, as reflected in plasma iron levels, is impaired in HH.
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