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Decreased hephaestin activity in the intestine of Copper-deficient mice causes systemic iron deficiency

Show simple item record Chen H. Huang G. Su T. Gao H. Attieh Z.K. McKie A.T. Anderson G.J. Vulpe C.D.
dc.contributor.editor 2006 2017-10-05T15:30:56Z 2017-10-05T15:30:56Z 2006
dc.identifier.issn 00223166
dc.description.abstract Copper and iron metabolism intersect in mammals. Copper deficiency simultaneously leads to decreased iron levels in some tissues and iron deficiency anemia, whereas it results in iron overload in other tissues such as the intestine and liver. The copper requirement of the multicopper ferroxidases hephaestin and ceruloplasmin likely explains this link between copper and iron homeostasis in mammals. We investigated the effect of in vivo and in vitro copper deficiency on hephaestin (Heph) expression and activity. C57BL-6J mice were separated into 2 groups on the day of parturition. One group was fed a copper-deficient diet and another was fed a control diet for 6 wk. Copper-deficient mice had significantly lower hephaestin and ceruloplasmin (∼50percent of controls) ferroxidase activity. Liver hepcidin expression was significantly downregulated by copper deficiency (∼60percent of controls), and enterocyte mRNA and protein levels of ferroportin1 were increased to 2.5 and 10 times, respectively, relative to controls, by copper deficiency, indicating a systemic iron deficiency in the copper-deficient mice. Interestingly, hephaestin protein levels were significantly decreased to ∼40percent of control, suggesting that decreased enterocyte copper content leads to decreased hephaestin synthesis and-or stability. We also examined the effect of copper deficiency on hephaestin in vitro in the HT29 cell line and found dramatically decreased hephaestin synthesis and activity. Both in vivo and in vitro studies indicate that copper is required for the proper processing and-or stability of hephaestin. © 2006 American Society for Nutrition.
dc.format.extent Pages: (1236-1241)
dc.language English
dc.publisher BETHESDA
dc.relation.ispartof Publication Name: Journal of Nutrition; Publication Year: 2006; Volume: 136; no. 5; Pages: (1236-1241);
dc.source Scopus
dc.title Decreased hephaestin activity in the intestine of Copper-deficient mice causes systemic iron deficiency
dc.type Article
dc.contributor.affiliation Chen, H., Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720-3104, United States
dc.contributor.affiliation Huang, G., Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720-3104, United States
dc.contributor.affiliation Su, T., Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720-3104, United States
dc.contributor.affiliation Gao, H., Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720-3104, United States
dc.contributor.affiliation Attieh, Z.K., Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720-3104, United States, Biochemistry Department, School of Medicine, American University, Beirut, Lebanon
dc.contributor.affiliation McKie, A.T., Department of Molecular Medicine, King's College, London SE59NU, United Kingdom
dc.contributor.affiliation Anderson, G.J., Queensland Institute of Medical Research, University of Queensland, Post Office Royal Brisbane Hospital, Brisbane, QLD 4029, Australia
dc.contributor.affiliation Vulpe, C.D., Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720-3104, United States
dc.contributor.authorAddress Vulpe, C.D.; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720-3104, United States; email:
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Biochemistry and Molecular Genetics;
dc.contributor.authorDepartment Biochemistry and Molecular Genetics
dc.contributor.faculty Faculty of Medicine
dc.contributor.authorInitials Chen, HJ
dc.contributor.authorInitials Huang, G
dc.contributor.authorInitials Su, T
dc.contributor.authorInitials Gao, H
dc.contributor.authorInitials Attieh, ZK
dc.contributor.authorInitials McKie, AT
dc.contributor.authorInitials Anderson, GJ
dc.contributor.authorInitials Vulpe, CD
dc.contributor.authorReprintAddress Vulpe, CD (reprint author), Univ Calif Berkeley, Dept Nutr Sci and Toxicol, Berkeley, CA 94720 USA.
dc.contributor.authorUniversity American University of Beirut Medical Center
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dc.description.citedCount 45
dc.description.citedTotWOSCount 50
dc.description.citedWOSCount 48
dc.format.extentCount 6
dc.identifier.coden JONUA
dc.identifier.pubmedID 16614410
dc.identifier.scopusID 33646386896
dc.publisher.address 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA
dc.relation.ispartOfISOAbbr J. Nutr.
dc.relation.ispartOfIssue 5
dc.relation.ispartofPubTitle Journal of Nutrition
dc.relation.ispartofPubTitleAbbr J. Nutr.
dc.relation.ispartOfVolume 136
dc.source.ID WOS:000237031400017
dc.type.publication Journal
dc.subject.otherAuthKeyword Ceruloplasmin
dc.subject.otherAuthKeyword Copper
dc.subject.otherAuthKeyword Ferroportin1
dc.subject.otherAuthKeyword Hephaestin
dc.subject.otherAuthKeyword Iron
dc.subject.otherChemCAS ceruloplasmin, 9031-37-2
dc.subject.otherChemCAS copper, 15158-11-9, 7440-50-8
dc.subject.otherChemCAS ferritin, 9007-73-2
dc.subject.otherChemCAS hepcidin, 342809-17-0
dc.subject.otherChemCAS iron, 14093-02-8, 53858-86-9, 7439-89-6
dc.subject.otherChemCAS Copper, 7440-50-8
dc.subject.otherChemCAS Heph protein, mouse
dc.subject.otherChemCAS Membrane Proteins
dc.subject.otherChemCAS Superoxide Dismutase, EC
dc.subject.otherIndex ceruloplasmin
dc.subject.otherIndex copper
dc.subject.otherIndex ferritin
dc.subject.otherIndex ferroportin 1
dc.subject.otherIndex hepcidin
dc.subject.otherIndex hephaestin
dc.subject.otherIndex iron
dc.subject.otherIndex messenger RNA
dc.subject.otherIndex unclassified drug
dc.subject.otherIndex animal tissue
dc.subject.otherIndex article
dc.subject.otherIndex cell culture
dc.subject.otherIndex colon adenocarcinoma
dc.subject.otherIndex copper deficiency
dc.subject.otherIndex copper metabolism
dc.subject.otherIndex human
dc.subject.otherIndex human cell
dc.subject.otherIndex iron deficiency
dc.subject.otherIndex iron metabolism
dc.subject.otherIndex labor induction
dc.subject.otherIndex mouse
dc.subject.otherIndex nonhuman
dc.subject.otherIndex protein expression
dc.subject.otherIndex tissue culture
dc.subject.otherIndex Anemia, Iron-Deficiency
dc.subject.otherIndex Animals
dc.subject.otherIndex Cell Line, Tumor
dc.subject.otherIndex Colonic Neoplasms
dc.subject.otherIndex Copper
dc.subject.otherIndex Female
dc.subject.otherIndex Humans
dc.subject.otherIndex Membrane Proteins
dc.subject.otherIndex Mice
dc.subject.otherIndex Mice, Inbred C57BL
dc.subject.otherIndex Pregnancy
dc.subject.otherIndex Reference Values
dc.subject.otherIndex Superoxide Dismutase
dc.subject.otherIndex Animalia
dc.subject.otherIndex Mammalia
dc.subject.otherKeywordPlus MULTICOPPER OXIDASE
dc.subject.otherKeywordPlus SUPEROXIDE-DISMUTASE
dc.subject.otherKeywordPlus GENE-EXPRESSION
dc.subject.otherKeywordPlus MALE RATS
dc.subject.otherKeywordPlus CERULOPLASMIN
dc.subject.otherKeywordPlus METABOLISM
dc.subject.otherKeywordPlus ABSORPTION
dc.subject.otherKeywordPlus HEPCIDIN
dc.subject.otherKeywordPlus PROTEIN
dc.subject.otherKeywordPlus FERROXIDASE
dc.subject.otherWOS Nutrition and Dietetics

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