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Generation of disease models for neurodegenerative disorders by deleting selenoprotein synthesis

Research Project

Project/Area Number 22790268
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionTohoku University

Principal Investigator

SUZUKI Takafumi  東北大学, 大学院・医学系研究科, 助教 (70508308)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords含セレン蛋白質 / SeCys-tRNA / 酸化ストレス / 抗酸化酵素 / Nrf2 / 神経変性
Research Abstract

We generated disease models for neurodegenerative disorders by deleting selenoproteins, a major member of antioxidant enzymes. We have found that transcriptional factor Nrf2 activate in the selenoprotein-deficient neuronal tissue. In the absence of Nrf2, selenoprotein deficiency in neuronal tissue cause severe degenerative phenotype. These results reveal that selenoproteins are essential for maintaining homeostasis of neuronal tissue, and that Nrf2 has cytoprotective role against loss of selenorpoteins.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (24 results)

All 2012 2011 2010 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (16 results) Remarks (1 results)

  • [Journal Article] Select heterozygous keap1 mutations have a dominant-negative effect on wild-type keap1 in vivo2011

    • Author(s)
      Suzuki T, Maher J, Yamamoto M.
    • Journal Title

      Cancer Res.

      Volume: 71 Pages: 986-996

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nrf2 and selenoproteins are essential for maintaining oxidative homeostasis in erythrocytes and protecting against hemolytic anemia2011

    • Author(s)
      Kawatani Y, Suzuki T, Shimizu R, Kelly VP, Yamamoto M
    • Journal Title

      Blood

      Volume: 117 Pages: 986-996

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nrf2 and selenoproteins are essential for maintaining oxidative homeostasis in erythrocytes and protecting against hemolytic anemia.2011

    • Author(s)
      Kawatani Y, Suzuki T, Shimizu R, Kelly VP, Yamamoto M.
    • Journal Title

      Blood

      Volume: 117 Pages: 986-996

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Select heterozygous keap1 mutations have a dominant-negative effect on wild-type keap1 in vivo.2011

    • Author(s)
      Suzuki T, Maher J, Yamamoto M.
    • Journal Title

      Cancer Res.

      Volume: 71 Pages: 1700-1709

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic analysis of cytoprotective functions supported by graded expression of Keap12010

    • Author(s)
      Taguchi K, Maher JM, Suzuki T, Kawatani Y, Motohashi H, Yamamoto M
    • Journal Title

      Mol Cell Biol.

      Volume: 30 Pages: 3016-3026

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Global downstream pathway analysis reveals a dependence of oncogenic NRF2 mutation on the mTOR growth signaling pathway2010

    • Author(s)
      Shibata T, Saito S, Kokubu A, Suzuki T, Yamamoto M and Hirohashi S
    • Journal Title

      Cancer Resarch

      Volume: 70 Pages: 9095-9105

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nrf2-deficiency creates a responsive microenvironment for metastasis to the lung2010

    • Author(s)
      Satoh H, Moriguchi T, Taguchi K, Takai J, Maher JM, Suzuki T, Winnard PT Jr, Raman V, Ebina M, Nukiwa T, Yamamoto M
    • Journal Title

      Carcinogenesis

      Volume: 31 Pages: 1833-1843

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] 4NQO誘発舌がんにおけるKeap1-Nrf2系の役割2012

    • Author(s)
      大越明、鈴木隆史、小林俊光、山本雅之
    • Organizer
      第147回日本耳鼻咽喉科学会宮城県地方部会学術講演会
    • Place of Presentation
      仙台
    • Year and Date
      2012-03-18
    • Related Report
      2011 Final Research Report
  • [Presentation] トランスジェニックマウスを用いたKeap1-Nrf2システムの機能解析2012

    • Author(s)
      鈴木隆史、山本雅之
    • Organizer
      東北大学Network Medicine GCOE冬の合宿2012
    • Place of Presentation
      秋保
    • Related Report
      2011 Final Research Report
  • [Presentation] Complementary Contribution of Nrf2 Gene Battery and Selenoproteins to Antioxidative Stress Response2011

    • Author(s)
      Takafumi Suzuki
    • Organizer
      Seminar of School of Biochemistry and Immunology Trinity College Dublin
    • Place of Presentation
      Dublin, Ireland.
    • Year and Date
      2011-01-27
    • Related Report
      2011 Final Research Report
  • [Presentation] 酸化ストレスによる神経疾患病態形成におけるKeap1-Nrf2系の役割の解明2011

    • Author(s)
      大越明、鈴木隆史、山本雅之
    • Organizer
      第4回リトリート大学院生研究発表会
    • Place of Presentation
      東北大学・片平さくらホール
    • Year and Date
      2011-01-15
    • Related Report
      2011 Final Research Report
  • [Presentation] マルチストレスセンサーKeap1の生理的機能解析2011

    • Author(s)
      高屋快、鈴木隆史、山本雅之
    • Organizer
      第4回リトリート大学院生研究発表会
    • Place of Presentation
      東北大学・片平さくらホール
    • Year and Date
      2011-01-15
    • Related Report
      2011 Final Research Report
  • [Presentation] 含セレン蛋白質とNrf2による酸化ストレス防御機構の脳発達時期における役割2011

    • Author(s)
      大越明、鈴木隆史、西島維知子、山本雅之
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Select heterozygous Keap1 mutations have a dominant-negative effect on wild-type Keap1 in vivo2011

    • Author(s)
      Takafumi Suzuki, Jonathan Maher, Masayuki Yamamoto
    • Organizer
      16th World Congress on Advances in Oncology and 14th International Symposium on Molecular Medicine
    • Place of Presentation
      Rhodes Island, Greece
    • Related Report
      2011 Final Research Report
  • [Presentation] マウス遺伝学解析に基盤とするKeap1-Nrf2システムの解明2011

    • Author(s)
      山本雅之、鈴木隆史、田口恵子、本橋ほづみ
    • Organizer
      第70回日本癌学会学術総会・名古屋国際会議場
    • Place of Presentation
      名古屋
    • Related Report
      2011 Final Research Report
  • [Presentation] Keap1による多様なストレス感知機構の実証2011

    • Author(s)
      高屋快、鈴木隆史、山本雅之
    • Organizer
      第84回日本生化学会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] Keap1による多様なストレス感知機構2011

    • Author(s)
      高屋快、鈴木隆史、本橋ほづみ、山本雅之
    • Organizer
      新学術領域研究「活性酸素シグナル」第6回班会議
    • Place of Presentation
      昭和薬科大学
    • Related Report
      2011 Final Research Report
  • [Presentation] THE NRF2-KEAP1 STRESS RESPONSE PATHWAY : MOLECULAR BASIS OF ADAPTIVE RESPONSES AND PATHOGENESIS2011

    • Author(s)
      Masayuki Yamamoto, Hirofumi Kurokawa, Takafumi Suzuki, Keiko Taguchi, Hozumi Motohashi
    • Organizer
      SOT's 50th Annual Meeting
    • Place of Presentation
      Walter E. Washington Convention Center in Washington, D. C.
    • Related Report
      2011 Final Research Report
  • [Presentation] Deletion of selenocysteine tRNA gene results in compensatory gene induction of cytoprotective enzymes by Nrf22010

    • Author(s)
      Takafumi Suzuki, Yukie Kawatani, Akira Okoshi, Vincent Kelly, Masayuki Yamamoto
    • Organizer
      9th international Symposium on Selenium in Biology and Medicine Selenium 2010
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] Complementary contribution of Nrf2 gene battery and selenoproteins to antioxidative stress response.2010

    • Author(s)
      Masayuki Yamamoto, Takafumi Suzuki, Yukie Kawatani, Vincent Kelly
    • Organizer
      9th international Symposium on Selenium in Biology and Medicine Selenium 2010
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] Cytoprotective systems of skin by selenoproteins and Nrf22010

    • Author(s)
      Mariko Takayama, Takafumi Suzuki, Kai Takaya, Ryuhei Okuyama and Masayuki Yamamoto
    • Organizer
      9th international Symposium on Selenium in Biology and Medicine Selenium 2010
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] Hematopoietic deficiency of Nrf2 and selenoproteins leads to severe defects in erythrocytes and lymphocytes2010

    • Author(s)
      Yukie Kawatani, Takafumi Suzuki, Vincent Kelly, and Masayuki Yamamoto
    • Organizer
      9th international Symposium on Selenium in Biology and Medicine Selenium 2010
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] Deletion of selenocysteine tRNA gene results in compensatory gene induction of cytoprotective enzymes by Nrf2.2010

    • Author(s)
      Suzuki T, Kawatani Y, Okoshi A, Kelly V, Yamamoto M
    • Organizer
      9th international Symposium on Selenium in Biology and Medicine Selenium 2010
    • Place of Presentation
      京都
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://dmbc.med.tohoku.ac.jp/official/index.html

    • Related Report
      2011 Final Research Report

URL: 

Published: 2010-08-23   Modified: 2016-04-21  

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