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In silico and in vitro evaluations of disruption of peroxisome proliferator-activated receptor alpha signaling pathway by emerging persistent organic pollutants

Research Project

Project/Area Number 16H05057
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental agriculture(including landscape science)
Research InstitutionEhime University

Principal Investigator

Ishibashi Hiroshi  愛媛大学, 農学研究科, 准教授 (90403857)

Co-Investigator(Kenkyū-buntansha) 有薗 幸司  熊本県立大学, 環境共生学部, 教授 (70128148)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
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)
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
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.

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。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (9 results)

All 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (3 results)

  • [Int'l Joint Research] Kyung Hee University(韓国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Kyung Hee University(韓国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] In Vitro and In Silico Evaluations of Binding Affinities of Perfluoroalkyl Substances to Baikal Seal and Human Peroxisome Proliferator-Activated Receptor α2019

    • Author(s)
      Hiroshi Ishibashi, Masashi Hirano, Eun-Young Kim, and Hisato Iwata
    • Journal Title

      Environmental Science & Technology

      Volume: 53 Issue: 4 Pages: 2181-2188

    • DOI

      10.1021/acs.est.8b07273

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] In vitro assessment of activation of Baikal seal (Pusa sibirica) peroxisome proliferator-activated receptor α by polybrominated diphenyl ethers2018

    • Author(s)
      Ishibashi, H., Kim, E.Y., Arizono, K., Iwata, H.
    • Journal Title

      Environmental Science and Technology

      Volume: 52 Pages: 11831-11837

    • DOI

      10.1021/acs.est.8b02501

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] In vitro and in silico evaluations of binding affinities of perfluoroalkyl substances to Baikal seal peroxisome proliferator-activated receptor α2019

    • Author(s)
      Ishibashi, H., Hirano, M., Kim, E.Y., Iwata, H.
    • Organizer
      Pollutant Responses in Marine Organisms 20 (PRIMO20)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新たな試験法の切り口:内分泌かく乱物質―核内受容体相互作用のin silico解析2018

    • Author(s)
      石橋弘志、平野将司、内田雅也、大倉美咲、石橋康弘、冨永伸明、岩田久人、有薗幸司
    • Organizer
      環境ホルモン学会 第21回研究発表会シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Remarks] バイカルアザラシPPARαに対する有機フッ素化合物の結合親和性

    • URL

      https://www.eurekalert.org/pub_releases/2019-03/eu-bao032719.php

    • Related Report
      2018 Annual Research Report
  • [Remarks] インビトロ/インシリコ解析系を用いたバイカルアザラシPPARαに対する有機フッ素化合物の結合評価

    • URL

      https://www.alphagalileo.org/Item-Display/ItemId/177124

    • Related Report
      2018 Annual Research Report
  • [Remarks] ロシアのバイアルアザラシにおける有機フッ素化合物の影響評価

    • URL

      http://researchsea.com/html/article.php/aid/12550/cid/1/research/science/ehime_university/investigating_how_chemicals_behave_in_russia_s_baikal_seals.html

    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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