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Activation of cellular signal transduction pathways in protective response to an atmospheric electrophile, 1,4-naphthoquinone

Research Project

Project/Area Number 24590159
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Environmental pharmacy
Research InstitutionUniversity of Tsukuba

Principal Investigator

YASUHIRO Shinkai  筑波大学, 医学医療系, 助教 (10454240)

Co-Investigator(Kenkyū-buntansha) KUMAGAI Yoshito  筑波大学, 医学医療系, 教授 (00250100)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords1,4-ナフトキノン / 親電子物質 / ストレス応答 / HSP/HSF1 / Keap1/Nrf2 / PTP1B/EGFR / 親電子シグナル / 細胞応答システム / 熱ショックタンパク質 / HSF1
Outline of Final Research Achievements

1,4-Naphthoquinone (1,4-NQ), an environmental electrophile, is capable of covalently binding to cellular proteins, which has been recognized to be associated with not only its toxicity but also the activation of cellular signal transduction pathways for cellular protection against reactive chemicals. In this study, we prepared specific anti-1,4-NQ antibody and found that 1,4-NQ-mediated covalent modification of heat shock protein 90 (HSP90) causes activation of heat shock factor-1 (HSF1), resulting in protection against 1,4-NQ toxicity in A431 cells. Furthermore, Keap1/Nrf2 and PTP1B/EGFR pathways as well as HSP90/HSF1 pathway also found to play a role in protective response to 1,4-NQ toxicity.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (16 results)

All 2015 2014 2013 2012 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (11 results) Remarks (2 results)

  • [Journal Article] Ambient Vapor Samples Activate the Nrf2-ARE Pathway in Human Bronchial Epithelial BEAS-2B Cells2014

    • Author(s)
      Yasuhiro Shinkai, Syun Nakajima, Arantza Eiguren-Fernandez, Emma Di Stefano, Debra A. Schmitz, John R. Froines, Arthur K. Cho, Yoshito Kumagai
    • Journal Title

      Environmental Toxicology

      Volume: 29 Pages: 1292-1300

    • DOI

      10.1002/tox.21860

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] <i>Garcinia vilersiana</i> bark extract activates the Nrf2/HO-1 signaling pathway in RAW264.7 cells2013

    • Author(s)
      Yasuhiro Shinkai, Ichiro Yamanaka, Ho Huynh Thuy Duong, Nguyen Thi Quynh, Yasunori Kanaho, Yoshito Kumagai
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 38 Issue: 6 Pages: 875-878

    • DOI

      10.2131/jts.38.875

    • NAID

      130004447090

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A method for detecting covalent modification of sensor proteins associated with 1,4-naphthoquinone-induced activation of electrophilic signal transduction pathways2012

    • Author(s)
      Hirose R, Miura T, Sha R, Shinkai Y, Tanaka-Kagawa T, Kumagai Y.
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 37 Issue: 5 Pages: 891-898

    • DOI

      10.2131/jts.37.891

    • NAID

      130004447003

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Reactive sulfur species-mediated activation of the Keap1-Nrf2 pathway by 1,2-napthoquinone through sulfenic acids formation under oxidative stress2015

    • Author(s)
      Yasuhiro Shinkai, Takashi Miura, Hidenao Kakehashi, Takaaki Akaike, Yoshito Kumagai
    • Organizer
      Society of Toxicology 54th Annual Meeting
    • Place of Presentation
      San Diego Convention Center(San Diego, USA)
    • Year and Date
      2015-03-22 – 2015-03-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 活性イオウ分子と活性酸素種が介在する可逆的な親電子シグナルの活性化2014

    • Author(s)
      新開泰弘、三浦高、掛橋秀直、赤池孝章、熊谷嘉人
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 活性イオウ分子と酸化ストレスを介した 1,2-ナフトキノンによる親電子シグナルの活性化2014

    • Author(s)
      新開泰弘、三浦高、掛橋秀直、赤池孝章、熊谷嘉人
    • Organizer
      フォーラム2014:衛生薬学・環境トキシコロジー
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Year and Date
      2014-09-19 – 2014-09-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 第41回日本毒性学会学術年会2014

    • Author(s)
      新開泰弘、吉田映子、Bruce A. FREEMAN、西田基宏、澤 智裕、赤池孝章、熊谷嘉人
    • Organizer
      神戸コンベンションセンター
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2014-07-02 – 2014-07-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] Activation of Nrf1/ARE pathway by cadmium in vascular endothelial cells2014

    • Author(s)
      Yasuhiro Shinkai, Toshiyuki Kaji, Yoshito Kumagai
    • Organizer
      The Environmental Response
    • Place of Presentation
      東北大学片平さくらホール(宮城県仙台市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 1,4ナフトキノンは親電子修飾を介して生存シグナル制御に関わるHSF90/HSF1系を活性化する2013

    • Author(s)
      新開泰弘、沙亮、熊谷嘉人
    • Organizer
      フォーラム2013:衛生薬学・環境トキシコロジー
    • Place of Presentation
      九州大学医学部百年講堂(福岡県福岡市)
    • Related Report
      2013 Research-status Report
  • [Presentation] メチル水銀とそのグルタチオン抱合体によるKeap1/Nrf2 経路の活性化

    • Author(s)
      新開泰弘、吉田映子、外山喬士、熊谷嘉人
    • Organizer
      平成25年度メチル水銀研究ミーティング
    • Place of Presentation
      LMJ東京研修センター(東京都文京区)
    • Related Report
      2013 Research-status Report
  • [Presentation] Activation of Heat Shock Response during exposure of human epithelial A431 cells to an environmental electrophile, 1,4-naphthoquinone

    • Author(s)
      Liang Sha
    • Organizer
      第12回分子予防環境医学研究会
    • Place of Presentation
      つくばサイエンス・インフォメーションセンター
    • Related Report
      2012 Research-status Report
  • [Presentation] 硫化水素産生酵素シスタチオニンβシンターゼによる細胞内親電子シグナル制御

    • Author(s)
      新開泰弘
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] シスタチオニンβシンターゼに由来するH2S/HS-は細胞内親電子シグナルを制御する

    • Author(s)
      新開泰弘
    • Organizer
      フォーラム2012 衛生薬学・環境トキシコロジー
    • Place of Presentation
      名古屋観光ホテル
    • Related Report
      2012 Research-status Report
  • [Presentation] 重金属毒性に対する防御応答システムを担うKeap1-Nrf2系

    • Author(s)
      新開泰弘
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台国際センター
    • Related Report
      2012 Research-status Report
  • [Remarks] 筑波大学医学医療系環境生物学研究室

    • URL

      http://www.md.tsukuba.ac.jp/environmental_medicine/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 環境生物学研究室ホームページ

    • URL

      http://www.md.tsukuba.ac.jp/environmental_medicine/index.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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