| Project/Area Number |
16H05057
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental agriculture(including landscape science)
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| Research Institution | Ehime University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
有薗 幸司 熊本県立大学, 環境共生学部, 教授 (70128148)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
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| Keywords | 残留性有機汚染物質 / 核内受容体 / 野生生物 / リスク評価 / 生態系保全 / 有機フッ素化合物 / 環境汚染物質 / 環境分析 / 生態系 |
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| Outline of Final Research Achievements |
This study assessed the binding affinities of perfluoroalkyl substances (PFASs) to the Baikal seal (Pusa sibirica; bs) and human (h) peroxisome proliferator-activated receptor α (PPARα) using in silico and in vitro assays. The in silico docking simulations revealed that the 1st ligand-binding pocket (LBP) of bsPPARα had higher affinities than that of hPPARα; however, the 2nd LBP of bsPPARα had lower affinities than that of hPPARα. An in vitro competitive binding assay showed that PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFHxS and PFOS could bind to recombinant bs and hPPARα LBD proteins. Interspecies comparison of the in vitro binding affinities revealed that bsPPARα had higher preference for PFASs with long carbon chains than that of hPPARα. Structure-activity relationship analyses suggested that the binding potencies of PFASs to PPARα might depend on LBP binding cavity volume, hydrogen bond interactions, the number of perfluorinated carbons, and the hydrophobicity of PFASs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で開発したヒト、水棲哺乳類および魚類PPARαを用いたインビトロ・インシリコアッセイ系により、各（野生）生物種の２種のPPARα LBPsに対するnew POPsの結合親和性の評価が可能となり、その種間差の要因が明らかになった。本研究の成果は、世界をリードする学術情報を発信するだけでなく、POPsに関するストックホルム条約等に関連した国際社会のニーズや生態系保全を考慮した化学物質の安全性評価・利用指針の構築に資することが期待される。
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