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Explanation of the mechanism that influence the cell sensitivity to the toxicity of methylmercury

Research Project

Project/Area Number 24249008
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionTohoku University

Principal Investigator

NAGANUMA AKIRA  東北大学, 薬学研究科(研究院), 教授 (80155952)

Co-Investigator(Kenkyū-buntansha) HWANG Gi-Wook  東北大学, 大学院薬学研究科, 講師 (00344680)
TAKAHASHI Tsutomu  東北大学, 大学院薬学研究科, 助教 (50186376)
高橋 勉  東北大学, 薬学研究科(研究院), 助教 (00400474)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥45,240,000 (Direct Cost: ¥34,800,000、Indirect Cost: ¥10,440,000)
Fiscal Year 2014: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2013: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
Fiscal Year 2012: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Keywordsメチル水銀 / 細胞毒性 / ユビキチン・プロテアソームシステム / 毒性増強機構 / 毒性軽減機構 / 培養細胞 / ユビキチン / プロテアソーム / 感受性決定因子 / ユビキチンプロテアソームシステム
Outline of Final Research Achievements

We have found that the ubiquitin proteasome (UP) system, which is an intracellular system involved in proteolysis, plays an important role in determination of the sensitivity of yeast cells to methylmercury. In the present study, we searched the enzymes, which affect the methylmercury toxicity, among enzymes involved in the UP system in human cells. As a result, we succeeded in identifying four kinds of ubiquitin transferases, ten kinds of de-ubiquitin enzymes, eight kinds of ubiquitin ligases and six kinds of F-box protein. In addition, we identified several kinds of proteins which participated in expression of the methylmercury toxicity from the proteins which are the substrate of the UP system.

Report

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

    (38 results)

All 2015 2014 2013 2012 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 2 results) Presentation (24 results) (of which Invited: 2 results) Book (2 results)

  • [Journal Article] The protein transportation pathway from Golgi to vacuoles via endosomes plays a role in enhancement of methylmercury toxicity2014

    • Author(s)
      Hwang G.W., Murai Y., Takahashi T., Naganuma A.
    • Journal Title

      Scientific Reports

      Volume: 4 Issue: 1 Pages: 5888-5888

    • DOI

      10.1038/srep05888

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CDC23 knockdown reinforces methylmercury sensitivity in HEK293 cells2014

    • Author(s)
      Du K., Takahashi T., Iwai-Shimada M., Miura N., Naganuma A., Hwang G.W.
    • Journal Title

      Fundam. Toxicol. Sci.

      Volume: 1 Pages: 161-164

    • NAID

      130005083345

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Brain-specific induction of secretoglobin 3A1 expression in mice treated with methylmercury2013

    • Author(s)
      Takahashi T, Kim MS, Saito T, Lee JY, Hwang GW, Naganuma A
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 38 Issue: 6 Pages: 963-965

    • DOI

      10.2131/jts.38.963

    • NAID

      130004447101

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low dose of methylmercury (MeHg) exposure induces caspase mediated-apoptosis in cultured neural progenitor cells2013

    • Author(s)
      Watanabe J, Nakamachi T, Ohtaki H, Naganuma A, Shioda S, Nakajo S
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 38 Issue: 6 Pages: 931-935

    • DOI

      10.2131/jts.38.931

    • NAID

      130004447097

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Global chemokine expression in methylmercury-treated mice: methylmercury induces brain-specific expression of CCL3 and CCL42013

    • Author(s)
      Kim MS, Takahashi T, Lee JY, Hwang GW, Naganuma A
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 38 Issue: 6 Pages: 925-929

    • DOI

      10.2131/jts.38.925

    • NAID

      130004447096

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Knockdown of the gene for homeobox protein HOXB13 reduces toxicity of oxidative-stress inducers in HEK293 cells2013

    • Author(s)
      Nakano R, Takahashi T, Naganuma A, Hwang GW
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 38 Issue: 6 Pages: 821-822

    • DOI

      10.2131/jts.38.821

    • NAID

      130004447084

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Changes in the levels of low molecular weight metabolites in the mouse cerebellum following treatment with methylmercury2013

    • Author(s)
      Hwang GW1, Lee JY, Kim MS, Sato M, Takahashi T, Naganuma A
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 38 Issue: 5 Pages: 703-706

    • DOI

      10.2131/jts.38.703

    • NAID

      10031191729

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deletion of the ubiquitin-conjugating enzyme Ubc2 confers resistance to methylmercury in budding yeast by promoting Whi2 degradation2013

    • Author(s)
      Hwang GW, Mastuyama F, Takahashi T, Lee JY, Naganuma A
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 38 Issue: 2 Pages: 301-303

    • DOI

      10.2131/jts.38.301

    • NAID

      10031151434

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methylmercury induces a brain-specific increase in chemokine CCL4 expression in mice2012

    • Author(s)
      J.Y. Lee, A. Naganuma
    • Journal Title

      J. Toxicol. Sci.

      Volume: 37 Pages: 1279-1282

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methylmercury induces CCL2 expression through activation of NF-kappaB in human 1321N1 astrocytes2012

    • Author(s)
      M.S. Kim, A. Naganuma
    • Journal Title

      J. Toxicol. Sci.

      Volume: 37 Pages: 1275-1278

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ubiquitin-conjugating enzyme Cdc34 mediates methylmercury resistance in Saccharomyces cerevisiae by increasing Whi2 degradation2012

    • Author(s)
      G.W. Hwang, A. Naganuma
    • Journal Title

      J. Toxicol. Sci.

      Volume: 37 Pages: 1283-1286

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of deubiquitinating enzymes involved in methylmercury toxicity in Saccharomyces cerevisiae2012

    • Author(s)
      G.W. Hwang, A. Naganuma
    • Journal Title

      J. Toxicol. Sci.

      Volume: 37 Pages: 1287-1290

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] メチル水銀毒性発現における細胞内ポリアミン代謝系の関与2015

    • Author(s)
      佐藤 昌幸, 永沼 章, 黄 基旭
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] ポリアミン合成系によるメチル水銀毒性軽減機構の解析2014

    • Author(s)
      佐藤昌幸、黄基旭、永沼章
    • Organizer
      第53回日本薬学会東北支部大会
    • Place of Presentation
      いわき市
    • Year and Date
      2014-10-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Brain-specific induction of expression of Ccl4 and Scgb3a1 by methylmercury in mice2014

    • Author(s)
      Min-Seok Kim, Tsutomu Takahashi, Jin-Yong Lee, Gi-Wook Hwang, Akira Naganuma
    • Organizer
      53th Annual Meeting of the Society of Toxicology
    • Place of Presentation
      Phoenix (USA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] ホメオボックス蛋白質HOX-B13が示すメチル水銀毒性増強におけるTNF-α の役割2013

    • Author(s)
      仲野 亮、福澤啓睦、黄 基旭、永沼 章
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      千葉市
    • Related Report
      2013 Annual Research Report
  • [Presentation] メチル水銀によってマウス脳特異的に発現誘導される遺伝子群2013

    • Author(s)
      金 ミンソク、斉藤隆寛、高橋 勉、李 辰竜、黄 基旭、永沼 章
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      千葉市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Methylmercury Induces a Brain-Specific Increase in Chemokine CCL3 and CCL4 Expression in Mice2013

    • Author(s)
      Min-Seok Kim, Jin-Yong Lee, Tsutomu Takahashi, Gi-Wook Hwang, Akira Naganuma
    • Organizer
      The XIII International Congress of Toxicology
    • Place of Presentation
      Seoul(Korea)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular mechanism by which homeobox protein HOX-B13 augments methylmercury toxicity in HEK293 cells2013

    • Author(s)
      Ryo Nakano, Gi-Wook Hwang, Akira Naganuma
    • Organizer
      The XIII International Congress of Toxicology
    • Place of Presentation
      Seoul(Korea)
    • Related Report
      2013 Annual Research Report
  • [Presentation] The function of TEX27 on reduction of methylmercury toxicity2013

    • Author(s)
      Seong-Eun Oh, Gi-Wook Hwang, Akira Naganuma
    • Organizer
      The XIII International Congress of Toxicology
    • Place of Presentation
      Seoul(Korea)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Screenings for Proteins that Influence Sensitivity of Cells to Methylmercury2013

    • Author(s)
      Akira Naganuma
    • Organizer
      The XIII International Congress of Toxicology
    • Place of Presentation
      Seoul(Korea)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] TNF-α/TNFR3シグナル伝達系を介したホメオボックス蛋白質HOXB13によるメチル水銀毒性増強機構2013

    • Author(s)
      仲野 亮、黄 基旭、永沼 章
    • Organizer
      フォーラム2013:衛生薬学・環境トキシコロジー
    • Place of Presentation
      福岡市
    • Related Report
      2013 Annual Research Report
  • [Presentation] マウス脳神経由来細胞におけるメチル水銀によるケモカインCCL4の発現誘導

    • Author(s)
      金ミンソク、李 辰竜、黄 基旭、高橋 勉、永沼 章
    • Organizer
      第52回日本薬学会東北支部大会
    • Place of Presentation
      仙台市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 酵母におけるAkr1によるMeh1のパルミチン酸化を介したメチル水銀毒性軽減作用に関わる分子機構の解明

    • Author(s)
      永沼 章
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report
  • [Presentation] HOXB13が示すメチル水銀毒性増強作用の分子機構解析

    • Author(s)
      永沼 章
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report
  • [Presentation] メチル水銀によってマウスの脳に特異的に発現誘導されるケモカイン

    • Author(s)
      永沼 章
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report
  • [Presentation] メチル水銀毒性と細胞内蛋白質トラフィッキング

    • Author(s)
      黄 基旭
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] The molecular mechanism underlying the reduction of methylmercury toxicity through the palmioylation of Meh1 by Akr1 in budding yeast

    • Author(s)
      永沼 章
    • Organizer
      The 6th International Congress of Asian Society of Toxicology
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report
  • [Presentation] Brain-specific expression of chemokines by methylmercury in mice

    • Author(s)
      永沼 章
    • Organizer
      The 6th International Congress of Asian Society of Toxicology
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report
  • [Presentation] マウス脳におけるメチル水銀によるケモカインの発現誘導

    • Author(s)
      金 ミンソク
    • Organizer
      第31回生体と金属・化学物質に関する研究会
    • Place of Presentation
      広島
    • Related Report
      2012 Annual Research Report
  • [Presentation] Ego complex のメチル水銀毒性軽減作用におけるMeh1 パルミチン酸化の関与

    • Author(s)
      永沼 章
    • Organizer
      第51回日本薬学会東北支部大会
    • Place of Presentation
      青森
    • Related Report
      2012 Annual Research Report
  • [Presentation] ホメオボックス蛋白質HOX-B13 が示すメチル水銀毒性増強作用の機構解析

    • Author(s)
      永沼 章
    • Organizer
      第12回分子予防環境医学研究会年会
    • Place of Presentation
      筑波
    • Related Report
      2012 Annual Research Report
  • [Presentation] メチル水銀毒性におけるパルミチン酸転移酵素群の役割

    • Author(s)
      黄 基旭
    • Organizer
      第2回重金属毒性機構解明に関する研究会
    • Place of Presentation
      十和田
    • Related Report
      2012 Annual Research Report
  • [Presentation] メチル水銀毒性発現における機能未知蛋白質TEX27の役割

    • Author(s)
      永沼 章
    • Organizer
      第2回重金属毒性機構解明に関する研究会
    • Place of Presentation
      十和田
    • Related Report
      2012 Annual Research Report
  • [Presentation] The palmitoylation of Meh1, a component of EGO complex, has an important role in the reduction of methylmercury toxicity in budding yeast

    • Author(s)
      永沼 章
    • Organizer
      52th Annual Meeting of the Society of Toxicology
    • Place of Presentation
      San Antonio, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] 動物モデルによるメチル水銀の生物影響評価:培養細胞系モデル

    • Author(s)
      黄 基旭
    • Organizer
      日本水産学会春期大会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Book] 毒性の科学2014

    • Author(s)
      永沼 章、黄 基旭(分担)
    • Total Pages
      200
    • Publisher
      東京大学出版会
    • Related Report
      2013 Annual Research Report
  • [Book] 魚食と健康 ―メチル水銀の生物影響―2014

    • Author(s)
      黄 基旭、永沼 章(分担)
    • Total Pages
      151
    • Publisher
      恒星社厚生閣
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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