Tohoku J. Exp. Med., 2002, 196 (1)

Review

Cellular Cadmium Uptake Mediated by the Transport System for Manganese

SEIICHIRO HIMENO, TAKAHIRO YANAGIYA,¹ SHUICHI ENOMOTO,¹
YUKIHIRO KONDO² and NOBUMASA IMURA

Kitasato University, School of Pharmaceutical Sciences, Department of Public Health and Molecular Toxicology, Tokyo 108-8641,
¹The Institute of Physical and Chemical Research (RIKEN), Wako 351-0198, and
²Nippon Medical School, Department of Urology, Tokyo 113-8602

The mechanism of cellular cadmium (Cd) uptake has been poorly understood. Recently, we developed Cd-resistant cell lines from metallothionein null mouse cells and showed that the Cd resistance of these cells was conferred primarily by a reduced Cd accumulation. Surprisingly, the uptake rate of manganese (Mn) was also markedly reduced in Cd-resistant cells. Subsequent studies on the kinetics of Cd and Mn uptake by Cd-resistant and parental cells revealed that the Mn transport system with high affinity for Mn is used for cellular Cd uptake, and that this pathway is suppressed in Cd-resistant metallothionein null cells. This is the first indication that the transport system for Mn is used for Cd uptake in mammalian cells. Divalent metal transporter 1 (DMT1) is the only known mammalian transporter involved in the uptake of both Cd and Mn. However, the high-affinity Mn/Cd transport system we found seems to be distinct from DMT1 because of the difference in optimal pH and substrate specificity. On the other hand, various types of Mn transporters have been shown to play an important role in cellular Cd uptake in non-mammalian species such as yeast, plants and bacteria, suggesting the existence of Mn transporters other than DMT1 in mammals.

Keywords —— cadmium; resistance; metallothionein; manganese; transport

© 2002 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2002, 196, 43-50

Address for reprints: Seiichiro Himeno, Department of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.

e-mail: himenos@pharm.kitasato-u.ac.jp

This paper was presented at the Sendai Symposium: Paradigm Shift in Heavy Metal Toxicology held on November 21-22, 2001.