Studies on toxic mechanism of metals

Researcher : Yorishige Imamura

　We found a rat strain exhibiting a strong resistance to cadmium (Cd)-induced lethality compared to other rat strains. To elucidate the molecular mechanism for Cd toxicity, the transport of the metal to various tissues has been compared between the Cd-resistant and ﾐsensitive rats. Several experimental results obtained so far suggest that zinc transporter plays a role in the strong resistance to Cd toxicity. We are currently investigating the structure and function of zinc transporter involved in Cd toxicity.

Research topics

1. Molecular mechanism for cadmium toxicity

2. Structure and function of zinc transporter

3. Molecular mechanism for combined toxicity of quinones with transition metals

References（２０００〜）

Takamure Y., Shimada H., Kiyozumi M., Yasutake A., Imamura Y. A possible mechanism of resistance to cadmium toxicity in male Long-Evans rats. Environ. Toxicol. Pharmacol., 21:231-234 (2006).

Shimada H, Nagano T, Funakoshi T, Imamura Y. Effects of chelating agents on distribution and excretion of terbium in mice. Toxicol. Mech. Methods, 15:181-184 (2005).

Shimada H, Takahashi M, Shimada A, Okawara T, Yasutake A, Imamura Y, Kiyozumi M. Protection from spontaneous hepatocellular　damage by N-benzyl-D-glucamine dithiocarbamate in Long-Evans Cinnamon rats, an animal model of Wilson's disease. Toxicol. Appl. Pharmacol. 202:59-67 (2005).

Shimada H, Takamure Y, Shimada A, Yasutake Y, Waalkes MP, Imamura Y. Strain differences of cadmium-induced hepatotoxicity in Wistar-Imamichi and Fischer 344 rats: involvement of cadmium accumulation. Toxicology 203:189-197 (2004).

Shimada H, Takamure Y, Imamura Y. Genetic evidence of resistance to cadmium toxicity in Wistar-Imamichi rats. J. Health Sci. 49: 316-318 (2003).

Kamenosomo T, Shimada H, Funakoshi T, Kojima S, Imamura Y. Structure-effect relationship in the mobilization of cadmium in mice by several dithiocarbamates. Comp. Biochem. Physiol. Part C 132: 61-66 (2002).

Shimada H, Nagano M, Yasutake A, Imamura Y. Wistar-Imamichi rats exhibit a strong resistance to cadmium toxicity. J. Health Sci. 48: 201-203 (2002).

Shimada H, Yamaguchi S, Murata H, Otagiri M, Imamura Y. Cadmium exposure decreases androgen-dependent metabolism of acetohexamide in liver microsomes of male rats through its testicular toxicity. Arch. Toxicol. 76: 8-12 (2002).