| Project/Area Number |
18H05293
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Review Section |
Broad Section K
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
上原 孝 岡山大学, 医歯薬学域, 教授 (00261321)
西田 基宏 九州大学, 薬学研究院, 教授 (90342641)
伊藤 昭博 東京薬科大学, 生命科学部, 教授 (40391859)
新開 泰弘 筑波大学, 医学医療系, 准教授 (10454240)
秋山 雅博 慶應義塾大学, 薬学部(芝共立), 特任講師 (60754570)
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| Project Period (FY) |
2018-06-11 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥195,260,000 (Direct Cost: ¥150,200,000、Indirect Cost: ¥45,060,000)
Fiscal Year 2022: ¥29,900,000 (Direct Cost: ¥23,000,000、Indirect Cost: ¥6,900,000)
Fiscal Year 2021: ¥29,900,000 (Direct Cost: ¥23,000,000、Indirect Cost: ¥6,900,000)
Fiscal Year 2020: ¥30,550,000 (Direct Cost: ¥23,500,000、Indirect Cost: ¥7,050,000)
Fiscal Year 2019: ¥41,860,000 (Direct Cost: ¥32,200,000、Indirect Cost: ¥9,660,000)
Fiscal Year 2018: ¥63,050,000 (Direct Cost: ¥48,500,000、Indirect Cost: ¥14,550,000)
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| Keywords | 環境中親電子物質 / 複合曝露 / エクスポソーム / タンパク質付加体 / レドックスシグナル系 / 活性イオウ分子 / 環境中親電子物 / アンチポーター / レドックスシグナル変動 / 毒性発現 / レドックスシグナル / イオウ付加体 / 生体内運命 |
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| Outline of Final Research Achievements |
Combined exposure of cultured cells and mice to environmental electrophiles was found to lower the activation of intracellular redox signaling and toxicity thresholds compared to single exposure. On the other hand, simultaneous exposure to reactive sulfur species that are able to capture environmental electrophiles, resulting in the formation of sulfur adducts repressed the adverse effects of environmental electrophiles. With methylmercury as a model of environmental electrophile, we also found that bismethylmercury sulfide, a sulfur adduct of methylmercury, spontaneously decomposition, leading to formation of dimethylmercury, which is excreted from the body through exhalation due to its high volatile species. Furthermore, when a variety of cells were exposed to sulfur stress, intracellular cysteine persulfide was shown to be excreted outside the cells via cystine-dependent antiporters.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は生活環境、ライフスタイルや食生活を介して、環境中親電子物質に日常的に複合曝露されている。したがって、今回の研究成果は当該物質の単独曝露に比べてリスクが上昇することを明快に示しており、今後のリスク評価の再考を促すものと言えよう。一方、環境中親電子物質のリスク増加がサルフェン硫黄を含む活性イオウ分子で制御できる可能性を示したことは意義深い。また、イオウストレスによりミトコンドリアの膜電位低下や筋肉や肝臓の萎縮を生じるが、それを回避する手段としてシスチン依存性アンチポーターを介して制御している知見を見出したことは学術的に意義がある。以上より、当初の研究目的は十分に達成されている。
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| Assessment Rating |
Ex-post Assessment Comments (Rating)
A: In light of the aim of introducing the research area into the research categories, expected outcomes of research have been produced.
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Assessment Rating |
Interim Assessment Comments (Rating)
A: In light of the aim of introducing the research area into the research categories, the expected progress has been made in research.
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