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Can tubulin be a novel target of toxicity of environmental chemicals ?

Research Project

Project/Area Number 24651061
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Risk sciences of radiation/Chemicals
Research InstitutionHiroshima University

Principal Investigator

KOTAKE Yaichiro  広島大学, 医歯薬保健学研究院(薬), 准教授 (20335649)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsチューブリン / 環境化学物質 / ユビキチン化 / ユビキチン化阻害
Research Abstract

Tubulin as a target of toxicity was limited to the case of disturbance of polimerization/depolymerization, and it was not expected that tubulin is a target in other cases. In the present study, we focused on tubulin as a target of toxicity and searched chemicals acting on tubulin. When we examined the effects of environmental chemicals on acetylation and ubiquitination of tubulin, we found chemicals inhibiting tubulin ubiquitination. Life extention of tubulin accompanied with the inhibition of ubiquitination will lead to cytotoxicity, and it raises the possibility that some kinds of environmental chemicals acts on tubulin and exerts the toxicity.

Report

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

    (18 results)

All 2014 2013 2012

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (11 results) (of which Invited: 2 results)

  • [Journal Article] Tributyltin-induced endoplasmic reticulum stress and its Ca^<2+>-mediated mechanism2013

    • Author(s)
      Isomura M, Kotake Y, Masuda K, Miyara M, Okuda K, Samizo S, Sanoh S, Hosoi T, Ozawa K, Ohta S
    • Journal Title

      Toxicol Appl Pharmacol

      Volume: 272(1) Issue: 1 Pages: 137-46

    • DOI

      10.1016/j.taap.2013.05.026

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of decreased glutamate receptor subunit GluR2 expression in lead-induced neuronal cell death2013

    • Author(s)
      Ishida K, Kotake Y, Miyara M, Aoki K, Sanoh S, Kanda Y, Ohta S
    • Journal Title

      J Toxicol Sci

      Volume: 38(3) Pages: 513-21

    • NAID

      10031158917

    • URL

      https://www.jstage.jst.go.jp/article/jts/38/3/38513/article

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] AMP-activated protein kinase-mediated glucose transport as a novel target of tributyltin in human embryonic carcinoma cells2013

    • Author(s)
      Yamada S, Kotake Y, Sekino Y, Kanda Y
    • Journal Title

      Metallomics

      Volume: 5(5) Issue: 5 Pages: 484-91

    • DOI

      10.1039/c3mt20268b

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of decreased glutamate receptor subunit GluR2 expression in lead-induced neuronal cell death.2013

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

      Journal of Toxicological Sciences

      Volume: 38 Pages: 513-521

    • NAID

      10031158917

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanisms of environmental organotin toxicity in mammals2012

    • Author(s)
      Kotake Y
    • Journal Title

      Biol Pharm Bull

      Volume: 35(11) Pages: 1876-80

    • NAID

      130001872281

    • URL

      https://www.jstage.jst.go.jp/article/bpb/35/11/35_b212017/_article

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy2012

    • Author(s)
      Klionsky DJ,・・・, Kotake Y,・・・, et al
    • Journal Title

      Autophagy

      Volume: 8(4) Pages: 445-544

    • URL

      https://www.landesbioscience.com/journals/autophagy/article/19496/?nocache=1671244998

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Predictability of metabolism of ibuprofen and naproxen using chimeric mice with human hepatocytes2012

    • Author(s)
      Sanoh S, Horiguchi A, Sugihara K, Kotake Y, Tayama Y, Uramaru N, Ohshita H, Tateno C, Horie T, Kitamura S, Ohta S
    • Journal Title

      Drug Metab Dispos

      Volume: 40(12) Issue: 12 Pages: 2267-72

    • DOI

      10.1124/dmd.112.047555

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] 低濃度MPP+によるオートファジー阻害を介した神経毒性メカニズムの解明2014

    • Author(s)
      宮良政嗣、古武弥一郎、太田茂
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 有機スズによるグルタミン酸受容体発現減少を介した神経影響2013

    • Author(s)
      古武弥一郎
    • Organizer
      メタルバイオサイエンス2013
    • Place of Presentation
      静岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Low concentration of Parkinson's disease-related neurotoxin MPP+ inhibits autophagy2013

    • Author(s)
      Miyara M, Kotake Y, Ohta S
    • Organizer
      The 13th International Congress of Toxicology
    • Place of Presentation
      ソウル(韓国)
    • Related Report
      2013 Final Research Report
  • [Presentation] パーキンソン病関連神経毒MPP+低濃度曝露によるオートファジー阻害2013

    • Author(s)
      宮良政嗣、古武弥一郎、太田茂
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      千葉
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Low concentration of Parkinson’s disease-related neurotoxin MPP+ inhibits autophagy.2013

    • Author(s)
      Miyara M, Kotake Y, Ohta S.
    • Organizer
      The 13th International Congress of Toxicology
    • Place of Presentation
      ソウル、韓国
    • Related Report
      2013 Annual Research Report
  • [Presentation] パーキンソン病関連化学物質による神経毒性メカニズムフォーラム2012

    • Author(s)
      古武弥一郎、幸田龍紀、宮良政嗣、太田茂
    • Organizer
      2012衛生薬学・環境トキシコロジー
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] パーキンソン病関連神経毒性物質によるチューブリンのユビキチン化阻害とオートファジー2012

    • Author(s)
      古武弥一郎
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Final Research Report
  • [Presentation] パーキンソン病関連神経毒性物質によるチューブリンのユビキチン化阻害とオートファジー2012

    • Author(s)
      古武 弥一郎
    • Organizer
      第39回日本毒性学会学術年会(招待講演)
    • Place of Presentation
      仙台
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Inhibition of autophagic flux induced by low concentration of 1-methyl-4-phenylpyridinium ion2012

    • Author(s)
      Miyara et al.
    • Organizer
      42th Society for Neuroscience
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] パーキンソン病関連化学物質による神経毒性メカニズム2012

    • Author(s)
      古武 弥一郎
    • Organizer
      フォーラム2012 衛生薬学・環境トキシコロジー(招待講演)
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Impairment of autophagy induced by low concentration of MPP+, a Parkinson's disease-related toxin2012

    • Author(s)
      Miyara et al.
    • Organizer
      The 6th International Symposium on Autophagy 2012
    • Place of Presentation
      Okinawa
    • Related Report
      2012 Research-status Report

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

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