Cadmium transport by human Nramp 2 expressed in Xenopus laevis oocytes

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 109Cd 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 μM 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 μM Cd 2+ by human Nramp2 was inhibited by metallothionein (IC50 = 0.14 μM). Therefore, human Nramp2 is suggested to function as a pH-dependent cadmium absorption transporter on the luminal membrane of human intestinal cells.