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Deregulation of proteins involved in iron metabolism in hepcidin-deficient mice

2005; Elsevier BV; Volume: 105; Issue: 12 Linguagem: Inglês

10.1182/blood-2004-12-4608

1528-0020

Lydie Viatte, Jeanne-Claire Lesbordes-Brion, Dan-Qing Lou, Myriam Bennoun, Gaël Nicolas, Axel Kahn, François Canonne‐Hergaux, Sophie Vaulont,

Hemoglobinopathies and Related Disorders

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. (Blood. 2005;105:4861-4864)