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 (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.
Okubo
Masato
M
Department of Therapeutics, Kyoritsu College of Pharmacy, Shibakoen 1-5-30, Minato-ku, Tokyo, 105-8512, Japan.
Yamada
Kyohei
K
Hosoyamada
Makoto
M
Shibasaki
Toshiaki
T
Endou
Hitoshi
H
D000818:Animals; D002104:Cadmium / Q000378:metabolism*; D002106:Cadmium Radioisotopes / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002413:Cations, Divalent / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000187:drug effects; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008668:Metallothionein / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014982:Xenopus laevis; D000099236:Solute Carrier Family 11, Member 2
D002104:Cadmium; D002106:Cadmium Radioisotopes; D027682:Cation Transport Proteins; D002413:Cations, Divalent; D033862:Iron-Binding Proteins; D008668:Metallothionein; D000099236:Solute Carrier Family 11, Member 2