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Elucidation of the mechanism of nanoparticle-induced biological effects focusing on epigenetic regulation

Research Project

Project/Area Number 16K01437
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical engineering assessment
Research InstitutionOsaka University

Principal Investigator

Higashisaka Kazuma  大阪大学, 医学系研究科, 特任講師(常勤) (20646757)

Research Collaborator Maki Ayaka  
Lin Ying  
Sato Kenta  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsDNAメチル化 / ナノ銀粒子 / プロテアソーム / ナノマテリアル / エピジェネティクス
Outline of Final Research Achievements

In this research, based on the new viewpoint of "epigenetic control by nanomaterial", we tried to analyze the nanomaterial-induced biological responses by analyzing the relationship between physical property-biological responses-epigenetic control. As a result, silver nanoparticles, which are used for things familiar to our lives, 1) decreased DNA methylation rate for human alveolar epithelial cell lines, and reduced a protein amount of DNA methylation enzyme, Dnmt1. In addition, 2) the decrease in the amount of Dnmt1 was resulted from proteasomal degradation by promoting ubiquitination of Dnmt1. Investigating the biological responses through epigenetic control can contribute to the identification of new biological responses induced by nanomaterials and the elucidation of its mechanism.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、エピジェネティクス制御をも考慮に入れた、ナノマテリアルの安全性評価手法やハザード回避手法の開発へと展開できるものと期待される。また、ナノマテリアルによるハザード発現機構の解明は、有用かつ安全なナノ医薬品の開発支援に資する基盤情報を提供することで、創薬プロセスの効率化に直結し、我が国のナノ医薬品開発を大きく推進させる原動力となる。従って本研究成果は、ナノ安全科学研究とも言うべきものであり、安全な薬物治療による疾病克服を実現し、国民に健康で安全な社会を提供すると共に、ナノ医薬品産業の国際競争力の強化をもたらすと予想される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2019 2018 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (4 results)

  • [Journal Article] Relationship between size and surface modification of silica particles and enhancement and suppression of inflammatory cytokine production by lipopolysaccharide or peptidoglycan stimulated RAW264.7 macrophages2016

    • Author(s)
      Uemura E., Yoshioka Y., Hirai T., Handa T., Nagano K., Higashisaka K., Tsutsumi Y.
    • Journal Title

      J. Nanopart. Res.

      Volume: 18 Issue: 6

    • DOI

      10.1007/s11051-016-3475-1

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 非晶質ナノシリカが精巣に及ぼす、エピジェネティックな変異を介したハザード同定2019

    • Author(s)
      佐藤建太, 東阪和馬, 衛藤舜一, 越田 葵, 小椋万生, 辻野博文, 長野一也, 堤 康央
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 食品関連製品に含まれるナノ素材の安全性評価~ナノ安全科学研究からナノ最適デザイン研究へ~2018

    • Author(s)
      東阪和馬, 長野一也, 松本博志, 堤 康央
    • Organizer
      第34回日本毒性病理学会(シンポジウム:ナノ化学物質の安全性評価と展望)
    • Related Report
      2017 Research-status Report
  • [Presentation] 銀ナノ粒子曝露がDNAメチル化へおよぼす影響解析2017

    • Author(s)
      東阪和馬, 真木彩花, 青山道彦, 桑形麻樹子, 齋藤 滋, 吉岡靖雄, 長野一也, 堤 康央
    • Organizer
      第44回日本毒性学会学術年会
    • Related Report
      2017 Research-status Report
  • [Presentation] ナノ銀粒子曝露によるDNAメチル化酵素への影響2016

    • Author(s)
      真木彩花, 東阪和馬, 青山道彦, 西川雄樹, 石坂拓也, 笠原淳平, 長野一也, 吉岡靖雄, 堤 康央
    • Organizer
      第43回日本毒性学会学術年会
    • Place of Presentation
      ウインクあいち(愛知県名古屋市)
    • Year and Date
      2016-06-29
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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