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Modulation and/or controlling of the aging event by the basic anti-oxidative response with environmental transcriptional factor Nrf1

Research Project

Project/Area Number 16H05922
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Applied health science
Research InstitutionSaga University

Principal Investigator

Tsujita Tadayuki  佐賀大学, 農学部, 講師 (20622046)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2016: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Keywords老化 / 酸化ストレス / Nrf1 / ストレス / 加齢・老化 / レドックスバランス
Outline of Final Research Achievements

We have been studying that the relationship between aging and environmental transcriptional factor, Nrf1, using genetical modified mouse and zebrafish. Especially, we have found that genetical aging model mice, Klotho-knockout mice with modulate the Nrf1 expression profile could live longer compared with single klotho knockout mice. Consequently, Klotho-/- :: Nrf1-knockdown mice were lived 20 weeks after birth. From those experiment we have identified 9 aging surrogate genetical marker which can explain the aging stage. We have tried to generate overexpress and/or knockout zebrafish model for those genes. As a consequence, we have already identified that serpina 4 and ccl4 knockout fish showed early aging phenotype. In addition, from metabolomic analysis compared with wild type, klotho knockout mouse and natural aging mice (over 3-years-old), we have identified that polyamine pathway have a several contribution to prevention of the aging phenotype.

Academic Significance and Societal Importance of the Research Achievements

タンパク質の機能不全は老化だけではなく、数々の疾患の原因となることが知られている。環境応答転写因子Nrf1はこれらの不良タンパク質除去に効果があると近年注目さレテいる。本研究では、老化によって蓄積することを見出したことから、Nrf1タンパク質量を是正することで老化が制御できることを遺伝的に明確にできたことは大きな成果といえる。現時点では、Nrf1の下流でどの標的遺伝子が真の老化抑制かを示すことはできていないが、今後、遺伝子改変動物を用いて老化現象を明確にし、そのタンパク質を制御する化合物や食品由来天然物を取得することにより、老化抑制のコンセプトを提唱することを目指している。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (20 results)

All 2018 2017 2016 Other

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 7 results,  Acknowledgement Compliant: 2 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-12018

    • Author(s)
      Kawaguchi Shin-Ichi, Gonda Yuhei, Yamamoto Takuya, Sato Yuki, Shinohara Hiroyuki, Kobiki Yohsuke, Ichimura Atsuhiko, Dan Takashi, Sonoda Motohiro, Miyata Toshio, Ogawa Akiya, Tsujita Tadayuki
    • Journal Title

      Molecules

      Volume: 23 Issue: 4 Pages: 885-885

    • DOI

      10.3390/molecules23040885

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] O-GlcNAcylation Signal Mediates Proteasome Inhibitor Resistance in Cancer Cells by Stabilizing NRF12018

    • Author(s)
      Sekine Hiroki、Okazaki Keito、Kato Koichiro、Alam M. Morshedul、Shima Hiroki、Katsuoka Fumiki、Tsujita Tadayuki、Suzuki Norio、Kobayashi Akira、Igarashi Kazuhiko、Yamamoto Masayuki、Motohashi Hozumi
    • Journal Title

      Molecular and Cellular Biology

      Volume: 38 Issue: 17 Pages: 00252-18

    • DOI

      10.1128/mcb.00252-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nrf2 activation attenuates genetic endoplasmic reticulum stress induced by a mutation in the phosphomannomutase 2 gene in zebrafish2018

    • Author(s)
      Mukaigasa Katsuki、Tsujita Tadayuki、Nguyen Vu Thanh、Li Li、Yagi Hirokazu、Fuse Yuji、Nakajima-Takagi Yaeko、Kato Koichi、Yamamoto Masayuki、Kobayashi Makoto
    • Journal Title

      Proc. Natl. Acad. Sci.

      Volume: 115 Issue: 11 Pages: 2758-2763

    • DOI

      10.1073/pnas.1714056115

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A ubiquitin-proteasome inhibitor bortezomib suppresses the expression of CYP11B2, a key enzyme of aldosterone synthesis2017

    • Author(s)
      Ito Ryo、Sato Ikuko、Tsujita Tadayuki、Yokoyama Atsushi、Sugawara Akira
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 489 Issue: 1 Pages: 21-28

    • DOI

      10.1016/j.bbrc.2017.05.109

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Time-resolved Fluorescent Detection for Glucose Using a Complex of Luminescent Layered Titanates and Enzymes2017

    • Author(s)
      SAKAGUCHI Yuki、MINAMIKAWA Tomoka、YAMAMURO Mayuko、TSUJITA Tadayuki、UEDA Toshihisa、KAMADA Kai、SOH Nobuaki
    • Journal Title

      Analytical Sciences

      Volume: 33 Issue: 9 Pages: 989-991

    • DOI

      10.2116/analsci.33.989

    • NAID

      130006071189

    • ISSN
      0910-6340, 1348-2246
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of erythropoietin gene expression in epithelial cells by chemicals identified in GATA inhibitor screenings2017

    • Author(s)
      Kaneko Hiroshi、Katoh Takehide、Hirano Ikuo、Hasegawa Atsushi、Tsujita Tadayuki、Yamamoto Masayuki、Shimizu Ritsuko
    • Journal Title

      Genes Cells

      Volume: 22 Issue: 11 Pages: 939-952

    • DOI

      10.1111/gtc.12537

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Homeostatic Shift Facilitates Endoplasmic Reticulum Proteostasis through Transcriptional Integration of Proteostatic Stress Response Pathways.2017

    • Author(s)
      Baird L, Tsujita T, Kobayashi E, Funayama R, Nagashima T, Nakayama K, and Yamamoto M.
    • Journal Title

      Mol Cell Biol

      Volume: 37 Issue: 4

    • DOI

      10.1128/mcb.00439-16

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation.2017

    • Author(s)
      Tsuchida K, Tsujita T, Hayashi M, Ojima A, Keleku-Lukwete N, Katsuoka F, Otsuki A, Kikuchi H, Oshima Y, Suzuki M, Yamamoto M.
    • Journal Title

      Free Radic Biol Med

      Volume: 103 Pages: 236-247

    • DOI

      10.1016/j.freeradbiomed.2016.12.041

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Intracellular thiol contents and fatty acid metabolism pathways are regulated by the Nrf1 (NFE2L1) with its transcriptional suppressor activity2016

    • Author(s)
      辻田 忠志
    • Journal Title

      生化学

      Volume: 88 Issue: 6 Pages: 776-781

    • DOI

      10.14952/SEIKAGAKU.2016.880776

    • NAID

      40021054408

    • ISSN
      0037-1017
    • Year and Date
      2016-12-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 転写因子Nrf1による生体恒常性維持機構の解明2018

    • Author(s)
      辻田忠志
    • Organizer
      第32回HiHA(広島大学健康長寿研究拠点)セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] HIF分解を制御するPHDタンパク質をアロステリックに阻害する新規化合物の探索2018

    • Author(s)
      園田健登, 廣津留倖一, 北川尚穂, 川口真一, 辻田忠志.
    • Organizer
      平成 30年度日本生化学会九州支部例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PHDタンパク質にアロステリックに作用し、低酸素応答因子HIFを安定化する新規化合物の探索2018

    • Author(s)
      園田健登, 廣津留倖一, 北川尚穂, 川口真一, 辻田忠志
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肝特異的Nrf1欠失マウスにおけるNAFLDとアクロレイン化タンパク質の関連解析2018

    • Author(s)
      谷内めぐみ, 井口瑶子, 辻田忠志.
    • Organizer
      日本ポリアミン学会第10回年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ストレス応答転写因子Nrf1を特異的に活性化する誘導剤の探索.2017

    • Author(s)
      福元雄大, 辻田 忠志.
    • Organizer
      平成 29年度日本生化学会九州支部例会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ストレス応答転写因子Nrf1を特異的に安定化する誘導剤の探索.2017

    • Author(s)
      福元 雄大, 辻田 忠志, 川口 真一.
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Possible link and future direction between stress transcriptional factor Nrf1/2 and NGLY12017

    • Author(s)
      Tadayuki TSUJITA
    • Organizer
      4th Global NGLY1 Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Nrf1タンパク質の活性化状態を直接モニターできるレポーター培養細胞による大規模化合物スクリーニングとNrf1に特異的な活性化化合物の創出2016

    • Author(s)
      辻田 忠志, Liam Baird, 古澤 祐樹, 勝岡 史樹, 彭 よしか, 後藤 智美, 川口 真一, 山本 雅之.
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 転写因子NRF1のOGT-HCF-1複合体を介した分解制御機構2016

    • Author(s)
      関根 弘樹, 加藤 幸一郎, 福田 愛菜, 鈴木 教郎, 岡崎 慶斗, アラム モシェッド. 辻田 忠志, 小林 聡, 山本 雅之, 本橋 ほづみ
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 環境転写因子Nrf1を特異的に活性化する化合物の探索2016

    • Author(s)
      廣津留 倖一, 川口 真一, 山本 雅之, 辻田 忠志.
    • Organizer
      第40回蛋白質と酵素の構造と機能に関する九州シンポジウム
    • Place of Presentation
      指宿
    • Year and Date
      2016-08-26
    • Related Report
      2016 Annual Research Report
  • [Remarks] 佐賀大学農学部生化学分野辻田忠グループのホームページ

    • URL

      http://seika.ag.saga-u.ac.jp

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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