Suppression of a high-affinity transport system for manganese in cadmium-resistant metallothionein-null cells.
Cadmium is a hazardous heavy metal existing ubiquitously in the environment, but the mechanism of cadmium transport into mammalian cells has been poorly understood. Recently, we have established a cadmium-resistant cell line (Cd-rB5) from immortalized metallothionein-null mouse cells, and found that Cd-rB5 cells exhibited a marked decrease in cadmium uptake. To investigate the mechanism of altered uptake of cadmium in Cd-rB5 cells, incorporation of various metals was determined simultaneously using a multitracer technique. Cd-rB5 cells exhibited a marked decrease in manganese incorporation as well as that of cadmium. However, the reduced uptake of manganese was observed only at low concentrations, suggesting that a high-affinity component of the Mn(2+) transport system was suppressed in Cd-rB5 cells. Competition experiments and kinetic analyses revealed that low concentrations of Cd(2+) and Mn(2+) share the same high-affinity pathway for their entry into cells. The mutual competition of Cd(2+) and Mn(2+) uptake was also observed in HeLa, PC12, and Caco-2 cells. The highest uptake of Cd(2+) and Mn(2+) by parental cells occurred at neutral pH, suggesting that this pathway is different from a divalent metal transporter 1 that can transport various divalent metals including Cd(2+) and Mn(2+) under acidic conditions. These results suggest that a high-affinity Mn(2+) transport system is used for mammalian cellular cadmium uptake, and that the suppression of this pathway caused a marked decrease in cadmium accumulation in cadmium-resistant metallothionein-null cells.
Yanagiya
T
T
Department of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Imura
N
N
Enomoto
S
S
Kondo
Y
Y
Himeno
S
S
D000818:Animals; D001692:Biological Transport; D002104:Cadmium / Q000378:metabolism*; D002460:Cell Line; D004351:Drug Resistance; D006863:Hydrogen-Ion Concentration; D008345:Manganese / Q000378:metabolism*; D008668:Metallothionein / Q000502:physiology*; D051379:Mice
D002104:Cadmium; D008345:Manganese; D008668:Metallothionein