title: Deregulation of proteins involved in iron metabolism in hepcidin-deficient mice.
abstract: Evidence is accumulating that hepcidin, a liver regulatory peptide, could be the common pathogenetic denominator of all forms of iron overload syndromes including HFE-related hemochromatosis, the most prevalent genetic disorder characterized by inappropriate iron absorption. To understand the mechanisms whereby hepcidin controls iron homeostasis in vivo, we have analyzed the level of iron-related proteins by Western blot and immunohistochemistry in hepcidin-deficient mice, a mouse model of severe hemochromatosis. These mice showed important increased levels of duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), and ferroportin compared with control mice. Interestingly, the level of ferroportin was coordinately up-regulated in the duodenum, the spleen, and the liver (predominantly in the Kupffer cells). Finally, we also evidenced a decrease of ceruloplasmin in the liver of hepcidin-deficient mice. We hypothesized that the deregulation of these proteins might be central in the pathogenesis of iron overload, providing key therapeutic targets for iron disorders.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale 567, Centre National de la Recherche Scientifique, et Université René Descartes, Faculté de Médecine Cochin-Port Royal, Paris, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Viatte
authors.forename: Jeanne-Claire
authors.initials: JC
authors.lastname: Lesbordes-Brion
authors.forename: Dan-Qing
authors.initials: DQ
authors.lastname: Lou
authors.forename: Myriam
authors.initials: M
authors.lastname: Bennoun
authors.forename: Gaël
authors.initials: G
authors.lastname: Nicolas
authors.forename: Axel
authors.initials: A
authors.lastname: Kahn
authors.forename: François
authors.initials: F
authors.lastname: Canonne-Hergaux
authors.forename: Sophie
authors.initials: S
authors.lastname: Vaulont
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000502:physiology*; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D045303:Cytochromes b / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004386:Duodenum / Q000378:metabolism; D005786:Gene Expression Regulation; D006432:Hemochromatosis; D064451:Hepcidins; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000235:genetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013154:Spleen / Q000378:metabolism; D019076:Transgenes; D015854:Up-Regulation; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D045303:Cytochromes b; D064451:Hepcidins; D007501:Iron; D033862:Iron-Binding Proteins; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C579599:Hamp protein, mouse