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Does adjusting Nrf1 active status lead to remediate reductive stress and aging-related diseases?

Research Project

Project/Area Number 25750357
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Applied health science
Research InstitutionTohoku University

Principal Investigator

TSUJITA Tadayuki  東北大学, 医学(系)研究科(研究院), 助教 (20622046)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsNrf1 / 老化 / 還元ストレス / NRF1 / グルタチオン
Outline of Final Research Achievements

We have identified that the expression levels of Nrf1 in aged mouse or aging model mouse (i.e., α-Klotho knockout mouse) were lower than young aged mice. Combination with our previous data that the liver from Nrf1 knockout mouse has higher thiol level, in this study, we trying to delay aging events under Nrf1 transcriptional control. Through our project, we succeed to reduce hysteric oxidative stress response that was induced through which Nrf2 over accumulation by increment the reductive status by Nrf1 over expression. We have proposed a concept that Nrf2 accumulation prevents by Nrf1, because Nrf1 has been competed with Nrf2 on antioxidative response element. We are continuing to confirm this anti-aging concept using a combinational effect with Nrf1 and Nrf2 in vivo.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (12 results)

All 2015 2014 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 3 results) Presentation (5 results) (of which Invited: 1 results) Book (1 results)

  • [Journal Article] Dnmt3a regulates osteoclast differentiation by coupling to an S-adenosyl methionine-producing metabolic pathway.2015

    • Author(s)
      Nishikawa et al.
    • Journal Title

      Nature Medicine

      Volume: 21 Issue: 3 Pages: 281-287

    • DOI

      10.1038/nm.3774

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Hypoxia-Sensitive Reporter System for High-Throughput Screening2015

    • Author(s)
      Tsujita, T.; Kawaguchi, S-i.; Dan, T.; Baird, L.; Miyata, T.; Yamamoto, M.
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 235 Issue: 2 Pages: 151-159

    • DOI

      10.1620/tjem.235.151

    • NAID

      130004822440

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Discovery of an NRF1-specific inducer from a large-scale chemical library using a direct NRF1-protein monitoring system.2015

    • Author(s)
      Tsujita T, Baird L, Furusawa Y, Katsuoka F, Hou Y, Gotoh S, Kawaguchi S-i, and Yamamoto M.
    • Journal Title

      Genes Cells

      Volume: 7 Issue: 7 Pages: 563-577

    • DOI

      10.1111/gtc.12248

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Loss of Nrf2 in mice evokes a congenital intrahepatic shunt that alters hepatic oxygen and protein expression gradients and toxicity.2014

    • Author(s)
      Skoko JJ, Wakabayashi N, Noda K, Kimura S, Tobita K, Shigemura N, Tsujita T, Yamamoto M, and Kensler TW.
    • Journal Title

      Toxicol Sci

      Volume: 141 Issue: 1 Pages: 112-119

    • DOI

      10.1093/toxsci/kfu109

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcription factor NF-E2-related factor 1 impairs glucose metabolism in mice.2014

    • Author(s)
      Hirotsu Y, Higashi C, Fukutomi T, Katsuoka F, Tsujita T, Yagishita Y, Matsuyama Y, Motohashi H, Uruno A, and Yamamoto M.
    • Journal Title

      Mol Cell Biol

      Volume: 19 Issue: 8 Pages: 650-665

    • DOI

      10.1111/gtc.12165

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcription factor Nrf1 negatively regulates the cystine/glutamate transporter and lipid-metabolizing enzymes2014

    • Author(s)
      Tsujita T, Peirce V, Baird L, Matsuyama Y, Takaku M, Walsh SV, Griffin JL, Uruno A, Yamamoto M, and Hayes JD.
    • Journal Title

      Mol Cell Biol

      Volume: 34 Issue: 20 Pages: 3800-3816

    • DOI

      10.1128/mcb.00110-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 転写因子Nrf1はシステイン・グルタミントランスポーターおよび脂質代謝酵素群を抑制制御する2014

    • Author(s)
      辻田 忠志, Vivian Mullin, Liam Baird, 松山 由香, 高久 美咲, Shawn Walsh, Julian Griffin, 山本 雅之, John Hayes
    • Organizer
      第25回日本生化学会大会
    • Place of Presentation
      京都国際会館(京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 転写因子Nrf1はシステイントランスポーターおよび脂質代謝酵素群を抑制制御する2014

    • Author(s)
      辻田 忠志, Vivian Mullin, Liam Baird, 松山 由香, 高久 美咲, Shawn Walsh, Julian Griffin, 山本 雅之, John Hayes.
    • Organizer
      第25回日本生体防御学会学術総会
    • Place of Presentation
      さくらホール(仙台市)
    • Year and Date
      2014-07-09 – 2014-07-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Transcription factor Nrf1 negatively regulates the cystine/glutamate transporter and lipid-metabolizing enzymes2014

    • Author(s)
      Tsujita T, Mullin V, Baird L, Matsuyama Y,Takaku M,Walsh SV,Griffin JL,Yamamoto M and Hayes JD
    • Organizer
      The Environmental Response IV
    • Place of Presentation
      Sendai, Japan
    • Related Report
      2013 Research-status Report
  • [Presentation] Transcription factor Nrf1 negatively regulates the cystine transporter and lipid metabolic enzymes to prevent over-nutrition in hepatocytes2014

    • Author(s)
      Tsujita T, Mullin V, Baird L, Matsuyama Y,Takaku M,Walsh SV,Griffin JL,Yamamoto M and Hayes JD
    • Organizer
      17th Biennial Meeting of Society for Free Radical Research International (SFRRI2014)
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2013 Research-status Report
  • [Presentation] 転写因子Nrf1はシステイントランスポーターおよび脂質代謝酵素群を抑制制御する

    • Author(s)
      辻田忠志
    • Organizer
      第56回脳研・高度先進合同セミナー(『心の遺伝子』研究コンソーシアム研究セミナー)
    • Place of Presentation
      青森県・弘前市・弘前大学医学部
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] 酸化ストレス認識分子基盤と創薬応用」生命科学から創薬へのイノベーション2014

    • Author(s)
      辻田 忠志, 山本 雅之
    • Total Pages
      202
    • Publisher
      南山堂
    • Related Report
      2014 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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