title: Heme carrier protein 1 transports heme and is involved in heme-Fe metabolism.
abstract: Heme-Fe is an important source of dietary iron in humans; however, the mechanism for heme-Fe uptake by enterocytes is poorly understood. Heme carrier protein 1 (HCP1) was originally identified as mediating heme-Fe transport although it later emerged that it was a folate transporter. We asked what happened to heme-Fe and folate uptake and the relative abundance of hcp1 and ho1 mRNA in Caco-2 cells after knockdown by transfection with HCP1-directed short hairpin (sh)RNA. Control Caco-2 cells were cultured in bicameral chambers with 0-80 μM heme-Fe for selected times. Intracellular Fe and heme concentration increased in Caco-2 cells reflecting higher external heme-Fe concentrations. Maximum Fe, heme, and heme oxygenase 1 (HO1) expression and activity were observed between 12 and 24 h of incubation. Quantitative RT-PCR for hcp1 revealed that its mRNA decreased at 20 μM heme-Fe while ho1 mRNA and activity increased. When shRNA knocked down hcp1 mRNA, heme-(55)Fe uptake and [(3)H]folate transport mirrored the mRNA decrease, ho1 mRNA increased, and flvcr mRNA was unchanged. These data argue that HCP1 is involved in low-affinity heme-Fe uptake not just in folate transport.
authors.affiliation: Micronutrient Laboratory, Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile.
authors.forename: Solange
authors.initials: S
authors.lastname: Le Blanc
authors.forename: Michael D
authors.initials: MD
authors.lastname: Garrick
authors.forename: Miguel
authors.initials: M
authors.lastname: Arredondo
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D020895:Enterocytes / Q000378:metabolism*; D005290:Ferric Compounds / Q000008:administration & dosage / Q000097:blood; D006418:Heme / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000378:metabolism*; D007504:Iron Radioisotopes; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D058979:Proton-Coupled Folate Transporter / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: C492690:FLVCR1 protein, human; D005290:Ferric Compounds; D007504:Iron Radioisotopes; D026901:Membrane Transport Proteins; D058979:Proton-Coupled Folate Transporter; D012333:RNA, Messenger; D011991:Receptors, Virus; C505058:SLC46A1 protein, human; D006418:Heme; C025314:ferric citrate; D007501:Iron; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1