Mechanism underlying the reduction of methylmercury toxicity by putrescine

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H02961
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Tohoku University
• Principal Investigator: Hwang Gi-Wook 東北大学, 薬学研究科, 准教授 (00344680)
• Co-Investigator(Kenkyū-buntansha): 外山 喬士 東北大学, 薬学研究科, 助教 (50720918)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: メチル水銀 / プトレシン / 毒性軽減

Outline of Final Research Achievements

We have previously found that the level of putrescine, a polyamine, was increased in the brains of mice administered methylmercury (MeHg), and addition of putrescine to culture medium reduced MeHg toxicity in C17.2 mouse neural stem cells. In this study, we investigated the role of ornithine decarboxylase (ODC), an enzyme involved in putrescine synthesis, in response to MeHg toxicity, and found that MeHg increased ODC activity in mouse cerebrum and cerebellum, but this increase was hardly observed in the kidney and liver, where MeHg accumulated at a high concentration. MeHg also increased the putrescine level and ODC enzyme activity in C17.2 cells, and these increases were due to the stabilization of the ODC enzyme by MeHg. We also found that putrescine suppressed apoptosis through mitochondrial dysfunction caused by MeHg. This is the first study to provide evidence that increased ODC activity may be a protective response against MeHg-induced neurotoxicity.

Free Research Field

分子毒性学

Academic Significance and Societal Importance of the Research Achievements

本研究では、生体が脳内に侵入したメチル水銀を感知し、それに応答してプトレシンレベルを増加させることによってその神経毒性から自身を防御している可能性を示した。これまで、プトレシンとメチル水銀毒性との関係について検討された例はなく、本研究成果のすべてが新事実となることは間違いない。本研究成果によって、未解明のままにされてきたメチル水銀毒性に対する生体防御機構を分子レベルで初めて説明することになり、遺伝的にメチル水銀に対して高感受性を示す人々の同定やそれらを考慮したメチル水銀毒性の正確な摂取基準の制定などに大きく貢献することが期待される。