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Gastroenterology. 2001 May;120(6):1420-9.

Intestinal iron uptake determined by divalent metal transporter is enhanced in HFE-deficient mice with hemochromatosis.

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1
University of Cambridge Department of Medicine, Addenbrooke's Hospital, Cambridge, England.

Abstract

BACKGROUND & AIMS:

Overexpression of duodenal divalent metal transporter (DMT1) messenger RNA occurs in hemochromatosis and HFE-knockout mice, suggesting that DMT1 mediates enhanced absorption of iron; however, increased expression of functional DMT1 protein has yet to be substantiated. We examined the role of DMT1 and the mucosal iron uptake defect in HFE-knockout mice.

METHODS:

Unidirectional iron uptake of 59Fe by small intestinal mucosa in vitro was compared between matched pairs of HFE-knockout and wild-type mice. DMT1-specific antibodies were used to block iron transport and to quantify duodenal protein expression.

RESULTS:

Ferrous iron uptake at 3.5-450 micromol/L was greatly enhanced in HFE-knockouts compared with wild-type, the apparent V(max) for Fe2+ transport being doubled (P < 0.01). Supplied as Fe3+, uptake was only enhanced in HFE-knockouts at < or =18 micromol/L, when the iron was almost completely converted to Fe2+ by mucosal ferrireductases. DMT1 antibody reduced the apparent Vmax for mucosal Fe2+ transport in HFE-knockouts to below wild-type control values (P < 0.02); immunoreactive mucosal DMT1 protein was increased nearly 2-fold in HFE-knockouts (P < 0.01).

CONCLUSIONS:

Disruption of the HFE gene up-regulates functional DMT1 transporters and enhances uptake of ferrous iron by this mechanism; DMT1 also mediates increased uptake after reduction of ferric iron presented at physiological concentrations.

PMID:
11313312
[Indexed for MEDLINE]
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