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Neurotoxicity of organotins via nuclear respiratory factor-1 (NRF-1) inhibition

Research Project

Project/Area Number 15H02826
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionHiroshima University

Principal Investigator

KOTAKE Yaichiro  広島大学, 大学院医歯薬保健学研究科(薬), 教授 (20335649)

Co-Investigator(Kenkyū-buntansha) 太田 茂  広島大学, 医歯薬保健学研究科(薬), 名誉教授 (60160503)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Keywords有機スズ / 核呼吸因子-1 / 神経毒性 / グルタミン酸受容体
Outline of Final Research Achievements

We revealed details about Nuclear Respiratory Factor-1 (NRF-1) inhibition by tributyltin, and clarified that suppressed NRF-1 expression is caused by hypermethylation of the NRF-1 promoter region. NRF-1 knockdown causes compensatory induction of lysosomal proteins, probably via suppression of lysosomal functions.

Academic Significance and Societal Importance of the Research Achievements

有機スズの神経毒性メカニズムは以前から報告されていたものの、そのメカニズムはほとんど明らかになっていなかった。今回低濃度有機スズの毒性メカニズムの一端に、NRF-1という転写因子の低下が関与すること、またなぜNRF-1が低下するのかを明らかにしたことは、環境中に広く存在する化学物質の毒性を明らかにし、その毒性を抑制する方法を考える上で興味深い知見である。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (7 results)

All 2018 2017 2016 2015

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (3 results)

  • [Journal Article] Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition2017

    • Author(s)
      Ishida Keishi、Aoki Kaori、Takishita Tomoko、Miyara Masatsugu、Sakamoto Shuichiro、Sanoh Seigo、Kimura Tomoki、Kanda Yasunari、Ohta Shigeru、Kotake Yaichiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 18 Issue: 8 Pages: 1754-1754

    • DOI

      10.3390/ijms18081754

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lead-Induced ERK Activation Is Mediated by GluR2 Non-containing AMPA Receptor in Cortical Neurons2017

    • Author(s)
      Ishida K, Kotake Y, Sanoh S, Ohta S.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 3 Pages: 303-309

    • DOI

      10.1248/bpb.b16-00784

    • NAID

      130005398478

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mild MPP(+) exposure impairs autophagic degradation through a novel lysosomal acidity-independent mechanism.2016

    • Author(s)
      Miyara M, Kotake Y, Tokunaga W, Sanoh S, Ohta S
    • Journal Title

      J Neurochem

      Volume: 139 Issue: 2 Pages: 294-308

    • DOI

      10.1111/jnc.13700

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Perfluorooctane sulfonate induces neuronal vulnerability by decreasing GluR2 expression.2016

    • Author(s)
      Ishida K., Tsuyama Y., Sanoh S., Ohta S., Kotake Y.
    • Journal Title

      Arch. Toxicol.

      Volume: 未定 Issue: 2 Pages: 885-895

    • DOI

      10.1007/s00204-016-1731-x

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] 核呼吸因子-1発現減少による網羅的な遺伝子発現変動2018

    • Author(s)
      齊木崇史,石田慶士,太田 茂,古武弥一郎
    • Organizer
      第45回日本毒性学会学術年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 低濃度トリブチルスズによるニューロン脆弱化機構の解明2015

    • Author(s)
      石田慶士、古武弥一郎、青木香織、瀧下智子、木村朋紀、諫田泰成、太田 茂
    • Organizer
      メタルバイオサイエンス研究会2015
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-08-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] 有機スズ神経毒性に関与する核呼吸因子-1 (NRF-1) 阻害機構の解明2015

    • Author(s)
      石田慶士、古武弥一郎、青木香織、瀧下智子、木村朋紀、諫田泰成、太田 茂
    • Organizer
      第42回日本毒性学会学術年会
    • Place of Presentation
      金沢市
    • Year and Date
      2015-06-29
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2020-03-30  

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