Nramp2 expression is associated with pH-dependent iron uptake across the apical membrane of human intestinal Caco-2 cells

The absorption of dietary non-heme iron by intestinal enterocytes is crucia l to the maintenance of body iron homeostasis. This process must be tightly regulated since there are no distinct mechanisms for the excretion of exce ss iron from the body. An insight into the cellular mechanisms has recently been provided by expression cloning of a divalent cation transporter (DCT1 ) from rat duodenum and positional cloning of its human homologue, Nramp2. Here we demonstrate that Nramp2 is expressed in the apical membrane of the human intestinal epithelial cell line, Caco 2 TC7, and is associated with f unctional iron transport in these cells with a substrate preference for iro n over other divalent cations. Iron transport occurs by a proton-dependent mechanism, exhibiting a concurrent intracellular acidification. Taken toget her, these data suggest that the expression of the Nramp2 transporter in hu man enterocytes may play an important role in intestinal iron absorption.