Tohoku J. Exp. Med., 2002, 196 (2)

Review

Investigation of Intracellular Factors Involved in Methylmercury Toxicity

AKIRA NAGANUMA, TAKEMITSU FURUCHI, NOBUHIKO MIURA,
GI-WOOK HWANG and SHUSUKE KUGE

Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences,
Tohoku University, Sendai 980-8578

Methylmercury is a known pollutant that causes severe central nervous system disorders. It is capable of passing through the blood-brain barrier and accumulates in cerebral cells. However, little is known regarding the mechanism of its toxicity at the molecular level. Using yeast cells, we searched for the genes involved in the expression of methylmercury toxicity, and found that genes encoding L-glutamine•D-fructose-6-phosphate amidotransferase (GFAT) and ubiquitin transferase (Ubc3) confer methylmercury resistance on the cells. It has also been shown that GFAT is the target molecule of methylmercury in yeast cells. These findings provide important clues about the mechanism underlying methylmercury toxicity in mammals.

Keywords —— methylmercury; resistance; yeast; ubiquitin; glucosamine-6-phosphate

© 2002 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2002, 196, 65-70

Address for reprints: Akira Naganuma, Ph.D., Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.

e-mail: naganuma@mail.pharm.tohoku.ac.jp

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