title: Differences in the uptake of iron from Fe(II) ascorbate and Fe(III) citrate by IEC-6 cells and the involvement of ferroportin/IREG-1/MTP-1/SLC40A1.
abstract: Dietary iron is present in the intestine as Fe(II) and Fe(III). Since enterocytes take up Fe(II) by the divalent metal transporter (DMT1), Fe(III) must be reduced. Whether other Fe(III) transport processes are present is unknown. Release of iron from the enterocyte into the plasma involves the iron-regulated transporter-1/metal transporter protein-1 (IREG-1/MTP-1, ferroportin) but ferroportin is also found on the apical membrane. We compared the uptake of iron from Fe(II):ascorbate and Fe(III):citrate using the rat intestinal enterocyte cell line-6 (IEC-6), in the presence of ferrous chelators, a blocking antibody to ferroportin, at different pH and during the over-expression of DMT1. Firstly, surface ferrireduction was absent. Secondly, blocking ferroportin partly and totally reduced Fe(II) and Fe(III) uptake, respectively. Thirdly, optimal Fe(II) uptake occurred at pH 5.5 but Fe(III) uptake was unaffected by pH and, fourthly, over-expression of DMT1 increased uptake of Fe(II) and Fe(III). This indicates that an increased extracellular H+ concentration facilitates DMT1-mediated Fe(II) uptake at the cell membrane. However, since Fe(III) uptake required DMT1, but not cell surface ferrireduction, and was independent of variations in extracellular pH, it appears that Fe(III) is internalised before ferrireduction and transport by DMT1. Ferroportin may function as a modulator of DMT1 activity and play a role in Fe(III) uptake, possibly by affecting the number or affinity of citrate binding sites.
authors.affiliation: Physiology, M311, School of Biomedical and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, WA 6009, Crawley, Australia.
authors.forename: Carla
authors.initials: C
authors.lastname: Thomas
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Oates
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D027682:Cation Transport Proteins / Q000378:metabolism*; D002460:Cell Line; D019343:Citric Acid / Q000494:pharmacology; D005290:Ferric Compounds / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D007422:Intestines / Q000166:cytology; D007501:Iron / Q000493:pharmacokinetics*; D007502:Iron Chelating Agents / Q000494:pharmacology; D033862:Iron-Binding Proteins / Q000378:metabolism; D051381:Rats; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D001205:Ascorbic Acid; D027682:Cation Transport Proteins; D019343:Citric Acid; D005290:Ferric Compounds; D007501:Iron; D007502:Iron Chelating Agents; D033862:Iron-Binding Proteins; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C025314:ferric citrate