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Research for mechanisms of control in gene expression under oxidative stress

Research Project

Project/Area Number 16K07260
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Molecular biology
Research InstitutionFukuoka Dental College

Principal Investigator

Ishii Takashi  福岡歯科大学, 口腔歯学部, 講師 (70516731)

Co-Investigator(Kenkyū-buntansha) 関口 猛  九州大学, 医学研究院, 助教 (60187846)
早川 浩  福岡歯科大学, 口腔歯学部, 教授 (70150422)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords酸化ストレス / RNA / 8-オキソグアニン / アポトーシス / PCBP1 / 神経変性疾患 / 老化 / 酸化損傷 / 8-oxoG / mRNA / mRNA分解 / 酸化RNA / AUF1 / 疾患 / Auf1
Outline of Final Research Achievements

Oxidative stress causes defect in gene expression, and eventually leads various diseases. Especially, mRNA oxidation induces neurodegeneretive disease and aging through the abnormal protein synthesis.
To avoid these crises, cells have to possess defense mechanisms for oxidative damage in mRNA. Then, we sought to isolate and identify factors which participate metabolism for oxidized RNA. As a result, we identified PCBP1 protein as an oxidized RNA-binding factor. PCBP1 participates induction of apoptosis under oxidative stress. This result indicates that cell possesses defense mechanism for RNA oxidation via apoptosis induction.

Academic Significance and Societal Importance of the Research Achievements

酸化ストレスは生命が逃れることのできないストレスであり、神経変性疾患や老化などの多くの疾患の原因となる。これらの疾患の発症は年齢と相関があり、老年病とも呼ばれている。わが国では超高齢化社会を迎え、老化関連疾患を抱える人口が爆発的に増加している。よって、酸化ストレスが一因となる老年病に対処する手立ての解明が、多くの国民に求められている。
本研究を通して、細胞が酸化ストレスを回避するための防御機構が明らかになった。本研究により得られた成果は、神経変性疾患や老化を防ぐための手立ての解明につながると考えている。

Report

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

    (6 results)

All 2018 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Specific binding of PCBP1 to heavily oxidized RNA to induce cell death2018

    • Author(s)
      Ishii Takashi、Hayakawa Hiroshi、Igawa Tatsuhiro、Sekiguchi Takeshi、Sekiguchi Mutsuo
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 115 Issue: 26 Pages: 6715-6720

    • DOI

      10.1073/pnas.1806912115

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] PCBP1タンパク質は酸化損傷RNA結合因子として機能する2018

    • Author(s)
      石井健士
    • Organizer
      日本遺伝学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Heavily oxidized RNA induces apoptosis2018

    • Author(s)
      Takashi Ishii
    • Organizer
      Beijing Symposium on Genetic Stability and Accurate Gene Expression under Oxidative Stress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] PCBP1タンパク質は重度の酸化損傷を受けたRNAを認識して細胞死を誘導する2018

    • Author(s)
      石井健士
    • Organizer
      日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 酸化損傷を受けたRNA鎖に結合する新規因子の同定2017

    • Author(s)
      石井健士
    • Organizer
      日本分子生物学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 酸化損傷mRNAの代謝に関わる新規因子の探索2016

    • Author(s)
      石井健士
    • Organizer
      日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report

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

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