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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3933-3939. Prepublished online as a Blood First Edition Paper on January 29, 2004; DOI 10.1182/blood-2003-09-3139. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-09-3139v1 103/10/3933    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 Chen, H. Articles by Vulpe, C. D. Search for Related Content PubMed PubMed Citation Articles by Chen, H. Articles by Vulpe, C. D. Related Collections Hematopoiesis and Stem Cells Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Hephaestin is a ferroxidase that maintains partial activity in sex-linked anemia mice Huijun Chen, Zouhair K. Attieh, Trent Su, Basharut A. Syed, Hua Gao, Rima M. Alaeddine, Tama C. Fox, Julnar Usta, Claire E. Naylor, Robert. W. Evans, Andrew T. McKie, Gregory J. Anderson, and Chris D. Vulpe From the Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA; Department of Health Sciences, The American University of Science and Technology, Beirut, Lebanon; Metalloprotein Research Group, The Randall Centre, King's College, London, United Kingdom; Department of Biochemistry, School of Medicine, The American University of Beirut, Beirut, Lebanon; Department of Crystallography, Birkbeck College, London, United Kingdom; Department of Molecular Medicine, King's College, London, United Kingdom; The Queensland Institute of Medical Research and the University of Queensland, Post Office Royal Brisbane Hospital, Brisbane, Queensland, Australia. Hephaestin (Hp) plays an important role in intestinal iron absorption and is predicted to be a ferroxidase based on significant sequence identity to the serum multicopper ferroxidase ceruloplasmin. Here, we demonstrate that Hp has both amine oxidase and ferroxidase activity in cultured cells and primary intestinal enterocytes with the use of both gel and solution assays. The specificity of the activity is shown by immunoblotting, immunoprecipitation, and immunodepletion experiments. Surprisingly, the truncated hephaestin expressed in sex-linked anemia (sla) mice still has measurable, but decreased, oxidase activity. Molecular modeling of the truncated hephaestin suggests retention of a minimum catalytic core required for enzymatic activity. We suggest that hephaestin, by way of its ferroxidase activity, facilitates iron export from intestinal enterocytes, most likely in cooperation with the basolateral iron transporter, Ireg1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Chen, G. Huang, T. Su, H. Gao, Z. K. Attieh, A. T. McKie, G. J. Anderson, and C. D. Vulpe Decreased Hephaestin Activity in the Intestine of Copper-Deficient Mice Causes Systemic Iron Deficiency J. Nutr., May 1, 2006; 136(5): 1236 - 1241. [Abstract] [Full Text] [PDF] M. Moriya and M. C. Linder Vesicular transport and apotransferrin in intestinal iron absorption, as shown in the Caco-2 cell model Am J Physiol Gastrointest Liver Physiol, February 1, 2006; 290(2): G301 - G309. [Abstract] [Full Text] [PDF] F. Canonne-Hergaux, A. Donovan, C. Delaby, H.-j. Wang, and P. Gros Comparative studies of duodenal and macrophage ferroportin proteins Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G156 - G163. [Abstract] [Full Text] [PDF] D. S. Kalinowski and D. R. Richardson The Evolution of Iron Chelators for the Treatment of Iron Overload Disease and Cancer Pharmacol. Rev., December 1, 2005; 57(4): 547 - 583. [Abstract] [Full Text] [PDF] R. S. Ohgami, D. R. Campagna, B. Antiochos, E. B. Wood, J. J. Sharp, J. E. Barker, and M. D. Fleming nm1054: a spontaneous, recessive, hypochromic, microcytic anemia mutation in the mouse Blood, November 15, 2005; 106(10): 3625 - 3631. [Abstract] [Full Text] [PDF] P. G. Reeves and L. C. S. DeMars Repletion of Copper-Deficient Rats with Dietary Copper Restores Duodenal Hephaestin Protein and Iron Absorption Experimental Biology and Medicine, May 1, 2005; 230(5): 320 - 325. [Abstract] [Full Text] [PDF] P. G. Reeves, L. C. S. DeMars, W. T. Johnson, and H. C. Lukaski Dietary Copper Deficiency Reduces Iron Absorption and Duodenal Enterocyte Hephaestin Protein in Male and Female Rats J. Nutr., January 1, 2005; 135(1): 92 - 98. [Abstract] [Full Text] [PDF] P. G. Reeves and L. C. S. DeMars Copper Deficiency Reduces Iron Absorption and Biological Half-Life in Male Rats J. Nutr., August 1, 2004; 134(8): 1953 - 1957. [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]

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