Research on methylmercury-induced selective cytotoxicity focusing on reactive sulfur species

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16368
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: National Institute for Minamata Disease
• Principal Investigator: Unoki Takamitsu 国立水俣病総合研究センター, その他部局等, 主任研究員 (00742868)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: メチル水銀 / 活性イオウ分子

Outline of Final Research Achievements

Brain sensitivity to methylmercury (MeHg) is developmentally and site-specific in both humans and rodents, but the mechanism is not well understood. Reactive sulfur species (RSS) are known to react with MeHg to form a less toxic metabolite, bismethylmercury sulfide, which exerts cytoprotective effects. In this study, we evaluated changes in RSS contents in rat brains and their relationships to sensitivity to MeHg. Analysis of fetal and juvenile rat brains revealed that RSS content was low in early development. Site-specific analysis of adult rat brains revealed that RSS levels in the cerebellum were lower than those in the hippocampus. In the cerebellum, the RSS levels in the granule cell layer were lower than those in the molecular layer. Thus, lower RSS levels corresponded to brain regions vulnerable to MeHg. Taken together with the result that brain RSS is consumed during MeHg exposure, RSS is a factor that defines the specificity of MeHg vulnerability in the brain.

Free Research Field

毒性学

Academic Significance and Societal Importance of the Research Achievements

メチル水銀による中枢神経系の細胞傷害は部位・細胞種や発達段階で異なるが、その特異性が生じる要因については全容の解明には至っていない。本研究は、活性イオウ分子を介したレドックスバランス制御の観点からこの疑問にアプローチすることで、メチル水銀毒性機序の解明を通とリスク評価への寄与が期待される。また、近年急速に発展しつつあるイオウ生物学において、活性イオウ分子の有する生理的意義付けに新たな知見を提供できる。