RT Journal Article
SR Electronic
T1 Suppression of a High-Affinity Transport System for Manganese in Cadmium-Resistant Metallothionein-Null Cells
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1080
OP 1086
VO 292
IS 3
A1 Takahiro Yanagiya
A1 Nobumasa Imura
A1 Shuichi Enomoto
A1 Yukihiro Kondo
A1 Seiichiro Himeno
YR 2000
UL http://jpet.aspetjournals.org/content/292/3/1080.abstract
AB 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 Mn2+ transport system was suppressed in Cd-rB5 cells. Competition experiments and kinetic analyses revealed that low concentrations of Cd2+ and Mn2+ share the same high-affinity pathway for their entry into cells. The mutual competition of Cd2+ and Mn2+ uptake was also observed in HeLa, PC12, and Caco-2 cells. The highest uptake of Cd2+ and Mn2+ 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 Cd2+ and Mn2+ under acidic conditions. These results suggest that a high-affinity Mn2+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. The American Society for Pharmacology and Experimental Therapeutics