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Okubo, M, Yamada, K, Hosoyamada, M, Shibasaki, T and Endou, H (2003) Cadmium transport by human Nramp 2 expressed in Xenopus laevis oocytes. Toxicol. Appl. Pharmacol. 187:162-7


Using the Xenopus oocyte expression system, human Nramp2, a human intestinal iron transporter, was shown to work as a cadmium transporter. An 1824-bp human Nramp2 cDNA was constructed by PCR cloning from reverse transcription products of human kidney mRNA. When the pH of the extracellular solution was 6.0, human Nramp2 transported (109)Cd(2+). Substitution of external Cl(-) with NO3- had no effect on human Nramp2-dependent cadmium uptake. The concentration-dependent Cd(2+) transport of human Nramp2 indicated Michaelis-Menten type transport with an average K(m) value of 1.04 +/- 0.13 microM and an average V(max) of 14.7 +/- 1.9 pmol/oocyte/h (n = 3). Cd(2+) transport via human Nramp2 was inhibited significantly by Cd(2+), Fe(2+), Pb(2+), Mn(2+), Cu(2+), and Ni(2+), while it was not inhibited by Hg(2+) and Zn(2+). Transport of 0.1 microM Cd(2+) by human Nramp2 was inhibited by metallothionein (IC50 = 0.14 microM). Therefore, human Nramp2 is suggested to function as a pH-dependent cadmium absorption transporter on the luminal membrane of human intestinal cells.




Animals; Cadmium/metabolism; Cadmium Radioisotopes/metabolism; Cation Transport Proteins/genetics; Cation Transport Proteins/metabolism; Cations, Divalent/pharmacology; Dose-Response Relationship, Drug; Gene Expression; Humans; Hydrogen-Ion Concentration; Ion Transport/drug effects; Iron-Binding Proteins/genetics; Iron-Binding Proteins/metabolism; Metallothionein/pharmacology; Oocytes/drug effects; Oocytes/metabolism; Time Factors; Xenopus laevis