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Prepublished online as a Blood First Edition Paper on May 1, 2003; DOI 10.1182/blood-2003-02-0347.
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Blood, 1 September 2003, Vol. 102, No. 5, pp. 1893-1899
RED CELLS
Systemic regulation of Hephaestin and Ireg1 revealed in studies of genetic and nutritional iron deficiency
Huijun Chen,
Trent Su,
Zouhair K. Attieh,
Tama C. Fox,
Andrew T. McKie,
Gregory J. Anderson, and
Chris D. Vulpe
From the Department of Nutritional Sciences and Toxicology, University of
California, Berkeley; Department of Molecular Medicine, King's College,
London, United Kingdom; and Joint Clinical Sciences Program, Queensland
Institute of Medical Research and University of Queensland, Royal Brisbane
Hospital, Brisbane, Queensland, Australia.
Hephaestin is a membrane-bound multicopper ferroxidase necessary for iron
egress from intestinal enterocytes into the circulation. Mice with sex-linked
anemia (sla) have a mutant form of Hephaestin and a defect in
intestinal basolateral iron transport, which results in iron deficiency and
anemia. Ireg1 (SLC11A3, also known as Ferroportin1 or Mtp1) is the putative
intestinal basolateral iron transporter. We compared iron levels and
expression of genes involved in iron uptake and storage in sla mice
and C57BL/6J mice fed iron-deficient, iron-overload, or control diets. Both
iron-deficient wild-type mice and sla mice showed increased
expression of Heph and Ireg1 mRNA, compared to controls,
whereas only iron-deficient wild-type mice had increased expression of the
brush border transporter Dmt1. Unlike iron-deficient mice, sla mouse
enterocytes accumulated nonheme iron and ferritin. These results indicate that
Dmt1 can be modulated by the enterocyte iron level, whereas
Hephaestin and Ireg1 expression respond to systemic rather than local signals
of iron status. Thus, the basolateral transport step appears to be the primary
site at which the small intestine responds to alterations in body iron
requirements.

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