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...

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Bibliographic Details
Published in:The Journal of pharmacology and experimental therapeutics 2000-03, Vol.292 (3), p.1080-1086
Main Authors: Yanagiya, T, Imura, N, Enomoto, S, Kondo, Y, Himeno, S
Format: Article
Language:English
Subjects:
Animals
Biological Transport
Cadmium - metabolism
Cell Line
Drug Resistance
Hydrogen-Ion Concentration
Manganese - metabolism
Metallothionein - physiology
Mice
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Summary: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.
ISSN:0022-3565
1521-0103