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

Gastroenterology
W J GriffithsT M Cox

Abstract

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. 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. 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). Disruption of the HFE gene up-regulates functional DMT1 transporters and enhances uptak...Continue Reading

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Citations

Apr 12, 2002·Proceedings of the National Academy of Sciences of the United States of America·Debbie TrinderEvan H Morgan
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