2021 Fiscal Year Final Research Report

Investigation of the defense mechanisms by the transcription factor TCF3 against methylmercury toxicity

Research Project

PDF

Project/Area Number	19H04276
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 63030:Chemical substance influence on environment-related
Research Institution	Tohoku Medical and Pharmaceutical University (2020-2021) Tohoku University (2019)
Principal Investigator	Hwang Gi-Wook 東北医科薬科大学, 薬学部, 教授 (00344680)
Co-Investigator(Kenkyū-buntansha)	進藤佐和子東北医科薬科大学, 薬学部, 助教 (50795987) 外山喬士東北大学, 薬学研究科, 助教 (50720918)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	メチル水銀 / TCF3 / SRXN1
Outline of Final Research Achievements	We previously identified TCF3 as a transcription factor that is activated in the brains of methylmercury-treated mice. In this study, we have shown that TCF3 inhibited the induction of apoptosis via mitochondrial damage as a novel protective factor against methylmercury-induced neurotoxicity. We also found that suppression of TCF3 degradation by proteasome is involved in TCF3 activation by methylmercury and that activated TCF3 is recruited to the promoter region of the SRXN1 gene, which encodes sulfiredoxin 1, thereby suppressing methylmercury-induced apoptosis. Furthermore, both TCF3 and SRXN1 were shown to be selectively increased in neurons in the brains of methylmercury-treated mice.
Free Research Field	分子毒性学
Academic Significance and Societal Importance of the Research Achievements	生体はメチル水銀の脳内侵入を感知するとTCF3活性化を介してSRXN1を発現誘導することでメチル水銀による神経毒性を軽減していることが初めて示唆された。これまで、TCF3/SRXN1経路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、本研究成果は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ものである。近年、低濃度のメチル水銀摂取による健康被害が世界的に懸念されていることから、メチル水銀に対して遺伝的に高感受性を示す人々の選定やそれらを考慮したメチル水銀の正確な摂取基準制定などに大きく貢献することが期待される。