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2012 Fiscal Year Final Research Report

Molecular mechanism of neuronal cell death induced by methyl mercury via endoplasmic reticulum stress

Research Project

  • PDF
Project/Area Number 22310039
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionOkayama University

Principal Investigator

UEHARA Takashi  岡山大学, 大学院・医歯薬学総合研究科, 教授 (00261321)

Project Period (FY) 2010 – 2012
Keywordsメチル水銀 / 一酸化窒素 / 酸化ストレス / 神経細胞 / アポトーシス / 経変性疾患 / シグナル伝達
Research Abstract

We found that methyl mercury results in neuronal cell death and the reduction of S-nitrosylated PDI formation in a concentration-dependent manner in SH-SY5Y cells. These observations suggested methyl mercury affects same cysteine residue that is oxidized by nitric oxide. Treatment with methyl mercury stimulated the specific splicing of XBP1 mRNA and phosphorylation of IRE1α. Thus, methyl mercury might induce apoptosis via endoplasmic reticulum stress caused by dysfunction of protein maturation system.

  • Research Products

    (20 results)

All 2013 2012 2011 2010 2009 Other

All Journal Article (5 results) Presentation (8 results) Book (6 results) Remarks (1 results)

  • [Journal Article] Participation of metabotropic glutamate receptors in pentetrazol-induced kindled seizure.2011

    • Author(s)
      Watanabe, Y., Kaida, Y., Fukuhara, S., Takechi, K., Uehara, T., and Kamei, C.
    • Journal Title

      Epilepsia

      Volume: 52 Pages: 140-150

    • DOI

      doi:10.1111/j.1528-1167.2010.02764.x.

  • [Journal Article] On-off system for PI3-kinase-Akt signaling through S-nitrosylation of PTEN.2011

    • Author(s)
      Numajiri, N., Takasawa, K., Nishiya, T., Tanaka, H., Ohno, K., Hayakawa, W., Asada, M., Matsuda, H., Azumi, K., Kamata, H., Nakamura, T., Hara, H., Minami, M., Lipton, S.A. and Uehara, T
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 108 Pages: 10349-10354

    • DOI

      doi:10.1073/pnas.1103503108

  • [Journal Article] Screening systems for identification of S-nitrosylated proteins.2011

    • Author(s)
      Uehara, T.and Nishiya, T.
    • Journal Title

      Nitric Oxide

      Volume: 25 Pages: 108-111

    • DOI

      doi:10.1016/j.niox.2010.11.002.

  • [Journal Article] The ECS (SPSB) E3 ubiquitin ligase is the master regulator of the lifetime of inducible nitric-oxide synthase2011

    • Author(s)
      Matsumoto, K., Nishiya, T., Maekawa, S., Horinouchi, T., Ogasawara, K., Uehara, T.,and Miwa, S..
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 409 Pages: 46-51

    • DOI

      doi:10.1016/j.bbrc.2011.04.103.

  • [Journal Article] SPRY domain-containing SOCS box protein-1 (SPSB1), SPSB2, and SPSB4 are master regulators of proteasome-dependent degradation of iNOS2011

    • Author(s)
      Nishiya, T., Matsumoto, K., Maekawa, S., Horinouchi, T., Fujimuro, M., Ogasawara, K., Uehara, T., and Miwa, S
    • Journal Title

      J. Biol. Chem

      Volume: 286 Pages: 9009-9019

    • DOI

      doi:10.1074/jbc.M110.190678.

  • [Presentation] ガス状分子の神経細胞死に対する作用機構2012

    • Author(s)
      上原 孝
    • 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
    • Year and Date
      2012-07-19
  • [Presentation] NOによる蛋白質修飾と神経細胞死制御2012

    • Author(s)
      上原 孝
    • Organizer
      第53回日本生化学会 中国・四国支部例会
    • Place of Presentation
      岡山大学
    • Year and Date
      2012-05-18
  • [Presentation] A novel modulatory 'on-off' system for PI 3-kinase-Akt signaling through S-nitrosylation2011

    • Author(s)
      上原 孝
    • Organizer
      第11回日本NO学会学術集会
    • Place of Presentation
      昭和薬科大学
    • Year and Date
      2011-05-14
  • [Presentation] 抗体アレイを使用した新規S-ニトロシル化蛋白質の探索2010

    • Author(s)
      上原 孝
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2010-12-09
  • [Presentation] Detection of oxidized protein-disulfide isomerase with a specific antibody2010

    • Author(s)
      Takashi Uehara
    • Organizer
      40th Annual Meeting Neuroscience 2010
    • Place of Presentation
      San Diego Convention Centre
    • Year and Date
      2010-11-15
  • [Presentation] ニトロソ化ストレスを切り口とした神経変性疾患の早期診断/治療薬開発へのアプローチ2010

    • Author(s)
      上原 孝
    • Organizer
      生体機能と創薬シンポジウム 2010京都
    • Place of Presentation
      グランヴィア京都
    • Year and Date
      2010-09-09
  • [Presentation] The life time of iNOS is regulated by the SPRY domain-containing SOCS box protein family linking iNOS to the elongin BC-Cul5-Rbx2 E3 ubiquitin ligase complex2010

    • Author(s)
      Tadashi Nishiya, Satoshi Maekawa, Masahiro Fujimuro, Kouetsu Ogasawara, Takashi Uehara, and Soichi Miwa
    • Organizer
      The 6thInternational Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric oxide
    • Place of Presentation
      The 6thInternational Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric oxide
    • Year and Date
      2010-06-17
  • [Presentation] Detection of oxidized ER protein by nitrosative/oxidative stress with a specific antibody2010

    • Author(s)
      Takashi Uehara
    • Organizer
      The 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric oxide
    • Place of Presentation
      京都
    • Year and Date
      2010-06-16
  • [Book] 一酸化窒素(NO)結合性(S-ニトロシル化)タンパク質の網羅的同定, 生化学85(1)2013

    • Author(s)
      上原 孝
    • Total Pages
      6
  • [Book] 小胞体内ニトロシル化による神経変性疾患の発症,脳212013

    • Author(s)
      上原 孝
    • Total Pages
      6
    • Publisher
      金芳堂
  • [Book] タンパク質ニトロシル化による細胞生死調節,実験医学30(17)2012

    • Author(s)
      上原 孝
    • Total Pages
      7
    • Publisher
      羊土社
  • [Book] 発癌/神経細胞の生死に関わる細胞内ROSシグナル制御,細胞工学31(2)2012

    • Author(s)
      鎌田英明,上原 孝
    • Total Pages
      6
    • Publisher
      秀潤社
  • [Book] NOはPI3-キナーゼ-Aktシグナルのスイッチ分子として機能している,実験医学29(18)2011

    • Author(s)
      上原 孝
    • Total Pages
      4
    • Publisher
      羊土社
  • [Book] NO・ニトロソ化シグナルと細胞死,実験医学27(15)2009

    • Author(s)
      上原 孝
    • Total Pages
      5
    • Publisher
      羊土社
  • [Remarks]

    • URL

      http://www.pharm.okayama-u.ac.jp/lab/yakuri/Uehara_Lab/Welcome.html

URL: 

Published: 2014-08-29  

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