Suppression of a high-affinity transport system for manganese in cadmium-resistant metallothionein-null cells

Takahiro Yanagiya, Nobumasa Imura, Shuichi Enomoto, Yukihiro Kondo, Seiichiro Himeno

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17 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1080-1086
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
Publication statusPublished - Mar 1 2000

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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