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Research on detoxification mechanism of environmental electrophiles mediated by reactive sulfur species

Research Project

Project/Area Number 16K18920
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Environmental and hygienic pharmacy
Research InstitutionUniversity of Tsukuba

Principal Investigator

UNOKI TAKAMITSU  筑波大学, 医学医療系, 特任助教 (00742868)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords活性イオウ分子 / 環境中新電子物質 / 環境中親電子物質 / 親電子物質 / 健康リスク / 環境 / 分析科学
Outline of Final Research Achievements

Environmental electrophiles such as 1,4-napthoquinone (1,4-NQ) and methylmercury easily bind to the protein thiols, thereby inducing cytotoxicity. In this study, we investigated the cytoprotective roles of reactive sulfur species, a highly nucleophilic compounds. We found that exposure of primary mouse hepatocytes to polysulfide and 1,4-NQ markedly decreased 1,4-NQ-mediated cell death and S-arylation of cellular proteins. Activation of cell survival signaling under exposure to 1,4-NQ was suppressed in the presence of polysulfides. These results suggest that reactive sulfur species act as a initial cytoprotective factor by capturing this electrophile.

Report

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

    (11 results)

All 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] The Capture of Cadmium by Reactive Polysulfides Attenuates Cadmium-Induced Adaptive Responses and Hepatotoxicity2017

    • Author(s)
      Akiyama Masahiro、Shinkai Yasuhiro、Unoki Takamitsu、Shim Ilseob、Ishii Isao、Kumagai Yoshito
    • Journal Title

      Chem Res Toxicol

      Volume: 30 Issue: 12 Pages: 2209-2217

    • DOI

      10.1021/acs.chemrestox.7b00278

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Polysulfide Na2S4 regulates the activation of PTEN/Akt/CREB signaling and cytotoxicity mediated by 1,4-naphthoquinone through formation of sulfur adducts2017

    • Author(s)
      Abiko Yumi、Shinkai Yasuhiro、Unoki Takamitsu、Hirose Reiko、Uehara Takashi、Kumagai Yoshito
    • Journal Title

      Scientific Report

      Volume: 7 Issue: 1 Pages: 4814-4814

    • DOI

      10.1038/s41598-017-04590-z

    • NAID

      120007128910

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 1,4-Naphthoquinone activates the HSP90/HSF1 pathway through the S-arylation of HSP90 in A431 cells: Negative regulation of the redox signal transduction pathway by persulfides/polysulfides2017

    • Author(s)
      Abiko Y, Sha L, Shinkai Y, Unoki T, Luong NC, Tsuchiya Y, Watanabe Y, Hirose R, Akaike T, Kumagai Y.
    • Journal Title

      Free Radic Biol Med

      Volume: 104 Pages: 118-128

    • DOI

      10.1016/j.freeradbiomed.2016.12.047

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Methylmercury, an environmental electrophile capable of activation and disruption of the Akt/CREB/Bcl-2 signal transduction pathway in SH-SY5Y cells2016

    • Author(s)
      Unoki T, Abiko Y, Toyama T, Uehara T, Tsuboi K, Nishida M, Kaji T, Kumagai Y.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 28944-28944

    • DOI

      10.1038/srep28944

    • NAID

      120007135346

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ポリスルフィドNa2S4はイオウ付加体形成を通じて1,4-NQによる PTEN/ Akt/CREB シグナルの活性化と細胞毒性を抑制する2017

    • Author(s)
      鵜木隆光、安孫子ユミ、新開泰弘、広瀬玲子、上原孝、熊谷嘉人
    • Organizer
      フォーラム2017:衛生薬学・環境トキシコロジー
    • Related Report
      2017 Annual Research Report
  • [Presentation] カドミウムによるHSP90の化学修飾を介した転写因子HSF1の活性化と活性イオウ分子によるその制御2017

    • Author(s)
      鵜木隆光、新開泰弘、増田章、秋山雅博、Ming XIAN、熊谷嘉人
    • Organizer
      第44回日本毒性学会学術年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] カドミウムによるHSP90の化学修飾を介する転写因子HSF1の活性化と活性イオウ分子によるその制御2017

    • Author(s)
      鵜木隆光、新開泰弘、増田章、秋山雅博、Xian Ming、熊谷嘉人
    • Organizer
      第70回日本酸化ストレス学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 1,4-Naphthoquinone-mediated activation of the HSP90/HSF1 signal transduction pathway and its negative regulation by reactive sulfur species in human A431 cells2016

    • Author(s)
      Unoki T, Shinkai Y, Sha L, Hirose R, Kumagai Y
    • Organizer
      IUTOX2016 XIV International Congress of Toxicology and X Mexican Congress of Toxicology
    • Place of Presentation
      メリダ(メキシコ)
    • Year and Date
      2016-10-02
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 親電子物質による生体影響の二面性:SH-SY5Y 細胞におけるメチル水銀曝露により生じるAkt/CREB/Bcl-2 経路の活性化と破綻2016

    • Author(s)
      鵜木隆光、安孫子ユミ、外山喬士、上原孝、坪井康次、西田基宏、鍜冶利幸、熊谷嘉人
    • Organizer
      フォーラム2016 衛生薬学・環境トキシコロジー
    • Place of Presentation
      昭和大学旗の台キャンパス(東京都・品川区)
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report
  • [Presentation] 1,4-ナフトキノンによるHSF90/HSF1経路の活性化と活性イオウ分子によるその制御2016

    • Author(s)
      鵜木隆光、新開泰弘、沙亮、広瀬玲子、熊谷嘉人
    • 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
  • [Presentation] Sodium tetrasulfide, a reactive sulfur species, protects cells from 1,4-naphthoquinone induced cytotoxicity through sulfur adduct formation2016

    • Author(s)
      Unoki T, Shinkai Y, Abiko Y, Hirose R, Kumagai Y
    • Organizer
      The 9th International Conference on the Biology, Chemistry , and Therapeutic Applications of Nitric Oxide. The 16th Annual Scientific Meeting of the Nitric Oxide Society of Japan
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2016-05-20
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2019-03-29  

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