Gut 2000;46:270-276 ( February )

Article

Localisation of divalent metal transporter 1 (DMT1) to the microvillus membrane of rat duodenal enterocytes in iron deficiency, but to hepatocytes in iron overload D Trinder^a, P S Oates^a, C Thomas^a, J Sadleir^b, E H Morgan^a

^a Department of Physiology, The University of Western Australia, Nedlands, Western Australia, Australia, ^b Department of Biochemistry, The University of Western Australia

Correspondence to: Dr D Trinder, Department of Biochemistry, The University of Western Australia, Nedlands, 6907, Western Australia, Australia

Accepted for publication 18 August 1999

BACKGROUNDThe mechanism of iron absorption by the intestine and its transfer to the main iron storage site, the liver, is poorly understood. Recently an iron carrier was cloned and named DMT1 (divalent metal transporter 1).
AIMSTo determine the level of DMT1 gene expression and protein distribution in duodenum and liver.
METHODSA DMT1 cRNA and antibody were produced and used in in situ hybridisation and immunohistochemistry, respectively, in rats in which the iron stores were altered by feeding diets with normal, low, and high iron content.
RESULTSDuodenal DMT1 mRNA was low in crypts and increased at the crypt-villus junction in iron deficient and control rats; it fell in the iron loaded state. Staining for DMT1 protein was not detected in crypts. In villus enterocytes, protein staining was localised to the microvillus membrane in iron deficiency, in the cytoplasm and to a lesser extent in the membrane in controls, and entirely in the cytoplasm of iron loaded animals. Liver DMT1 mRNA was distributed evenly across hepatocytes. DMT1 protein staining was observed on hepatocyte plasma membranes, with highest values in the iron loaded state, lower values in control animals, and none after iron depletion.
CONCLUSIONSResults are consistent with a role for DMT1 in the transmembrane transport of non-transferrin bound iron from the intestinal lumen and from the portal blood.


Keywords: DMT1; iron transporters; iron absorption; duodenum; liver

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