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Probing ROS signaling with small molecules

Planned Research

Project AreaSignaling functions of reactive oxygen species
Project/Area Number 20117006
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTohoku University

Principal Investigator

ARIMOTO HIROKAZU (ARIMOTO Hirokazu)  東北大学, 生命科学研究科, 教授 (60262789)

Project Period (FY) 2008-11-13 – 2013-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥105,690,000 (Direct Cost: ¥81,300,000、Indirect Cost: ¥24,390,000)
Fiscal Year 2012: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2011: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2010: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000)
Fiscal Year 2009: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000)
Fiscal Year 2008: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Keywords活性酸素 / 化学プローブ / 一酸化窒素 / 8-ニトロcGMP / オートファジー / ニトロcGMP / 内因性物質 / ケミカルバイオロジー / ニトロ化
Research Abstract

8-Nitro-cGMP is a novel mediator of active oxygen and nitric oxide. In this program, isotopically labeled 8- nitro-cGMP was synthesized to examine its metabolic fate in cells. It was reduced to 8-amino-cGMP first, and then converted to intact cGMP in cells. The latter transformation from 8-amino-cGMP required LPS-treatment of cells. We also prepared fluorescent nitroguanosine probes to obtain insight into the intracellular localization of 8-nitro-cGMP. The lysosomal localization of the fluorescent probes prompted us to examine the roles of 8-nitro-cGMP in autophagy induction. 8-Nitro-cGMP accelerated the autophagic clearance of intracellular group A Streptococcus (GAS). Interestingly, the surface of intracellular GAS was modified by S-guanylation, and the level of the modification showed a robust relationship with GAS ubiquitination suggesting that S-guanylation. These results may suggest that 8-nitro-cGMP works as a tag for selective transport of bacteria to autophagosomes.

Report

(7 results)
  • 2013 Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report   Self-evaluation Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (35 results)

All 2014 2013 2012 2011 2010 2009 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (19 results) (of which Invited: 3 results) Remarks (7 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Endogenous nitrated nucleotide is a key mediator of autophagy and innate defense against bacteria.2013

    • Author(s)
      Ito C, Saito Y, Nozawa T, Fujii S, Sawa T, Inoue H, Matsunaga T, Khan S, Akashi S, Hashimoto R, Aikawa C, Takahashi E, Sagara H, Komatsu M, Tanaka K, Akaike T, Nakagawa I, Arimoto H.
    • Journal Title

      Mol. Cell

      Volume: 52 Issue: 6 Pages: 794-804

    • DOI

      10.1016/j.molcel.2013.10.024

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fluorescent probes for live cell imaging of endogenous guanine nitration2013

    • Author(s)
      Saito Y, Ito C, Fujii S, Sawa T, Akaike T and Arimoto H.
    • Journal Title

      Chembiochem.

      Volume: 14 Issue: 9 Pages: 1068-1071

    • DOI

      10.1002/cbic.201300129

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nitric oxide promotes recycling of 8-nitro-cGMP, a cytoprotectivemediator, into intact cGMP in cells2012

    • Author(s)
      Yohei Saito, Tomohiro Sawa, Jun Yoshitake, Chiaki Ito, Shigemoto Fujii, Takaaki Akaike and Hirokazu Arimoto
    • Journal Title

      Moi BioSyst

      Volume: 8 Issue: 11 Pages: 2909-2915

    • DOI

      10.1039/c2mb25189b

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of redox signaling involving chemical conjugation of protein thiols by nitric oxide and electrophiles2010

    • Author(s)
      Sawa T, Arimoto H, and Akaike T
    • Journal Title

      Bioconjugate Chem

      Volume: 21 Issue: 7 Pages: 1121-1129

    • DOI

      10.1021/bc900396u

    • Related Report
      2013 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Redox Signaling Involving Chemical Conjugation of Protein Thiols by Nitric Oxide and Electrophiles2010

    • Author(s)
      T.Sawa, H.Arimoto, T.Akaike
    • Journal Title

      Bioconjugate Chem. 21巻

      Pages: 1121-1129

    • Related Report
      2010 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Regulation of Redox Signaling Involving Chemical Conjugation of Protein Thiols by Nitric Oxide and Electrophiles2010

    • Author(s)
      澤智裕, 有本博一, 赤池孝章
    • Journal Title

      Bioconjugate Chemistry 21(印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] チオール基の修飾による活性酸素のセンサー機能制御2009

    • Author(s)
      澤智裕、有本博一、赤池孝章
    • Journal Title

      実験医学増刊:病態解明に迫る活性酸素シグナルと酸化ストレス

      Pages: 2341-2347

    • Related Report
      2010 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] チオール基の修飾による活性酸素のセンサー機能制御2009

    • Author(s)
      澤智裕, 有本博一, 赤池孝章
    • Journal Title

      実験医学増刊 27

      Pages: 2341-2347

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Endogenous Nitrated Nucleotide Is a Key Mediator of Autophagy and Innate Defense against Bacteria2014

    • Author(s)
      Arimoto, H
    • Organizer
      Gordon Research Conference : Autophagy in Stress Development & Disease
    • Place of Presentation
      Lucca, Italy
    • Year and Date
      2014-03-19
    • Related Report
      2013 Final Research Report
  • [Presentation] 感染症の制御に向けた化学からのアプローチ2012

    • Author(s)
      有本博一
    • Organizer
      中西シンポジウム2012
    • Place of Presentation
      慶応義塾大学 (横浜市)
    • Year and Date
      2012-03-25
    • Related Report
      2013 Final Research Report
  • [Presentation] 感染症の理解と制御のための化学的アプローチ2011

    • Author(s)
      有本博一
    • Organizer
      第13回生命化学研究会
    • Place of Presentation
      仙台市ホテル佐勘
    • Year and Date
      2011-01-08
    • Related Report
      2013 Final Research Report 2010 Annual Research Report
  • [Presentation] 感染症の理解と制御のための化学的アプローチ2010

    • Author(s)
      有本博一
    • Organizer
      神奈川大学工学部学術フロンティアプロジェクト公開シンポジウム
    • Place of Presentation
      横浜市神奈川大学横浜キャンパス
    • Year and Date
      2010-10-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Discovery and Functions of Novel cGMP derivative2010

    • Author(s)
      H.Arimoto
    • Organizer
      東北大学GCOE サマースクール2010
    • Place of Presentation
      東北大学大学院理学研究科(基調講演)
    • Year and Date
      2010-08-19
    • Related Report
      2010 Self-evaluation Report
  • [Presentation] Discovery and Functions of Novel cGMP derivative2010

    • Author(s)
      有本博一
    • Organizer
      東北大学GCOEサマースクール2010
    • Place of Presentation
      仙台市東北大学理学部
    • Year and Date
      2010-08-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] 感染症の理解と制御のための化学的アプローチ2010

    • Author(s)
      有本博一
    • Organizer
      第22回万有札幌シンポジウム
    • Place of Presentation
      札幌市さっぽろ芸術文化の館
    • Year and Date
      2010-07-03
    • Related Report
      2013 Final Research Report 2010 Annual Research Report
  • [Presentation] 感染症の理解と制御のための化学的アプローチ2010

    • Author(s)
      有本博一
    • Organizer
      第22回万有札幌シンポジウム
    • Place of Presentation
      さっぽろ芸術文化の館(招待講演)
    • Year and Date
      2010-07-03
    • Related Report
      2010 Self-evaluation Report
  • [Presentation] Chemical studies on protein modifications by nitronucleotides2010

    • Author(s)
      H.Arimoto
    • Organizer
      The 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
    • Year and Date
      2010-06-15
    • Related Report
      2010 Self-evaluation Report
  • [Presentation] ニトロ化ヌクレオチドのケミカルバイオロジー2010

    • Author(s)
      有本博一
    • Organizer
      日本化学会第90春季年会
    • Place of Presentation
      近畿大学本部キャンパス(特別講演)
    • Year and Date
      2010-03-29
    • Related Report
      2010 Self-evaluation Report
  • [Presentation] ニトロ化ヌクレオチドのケミカルバイオロジー2010

    • Author(s)
      有本博一
    • Organizer
      日本化学会 第90春季年会
    • Place of Presentation
      近畿大学 本部キャンパス(大阪府東大阪市)
    • Year and Date
      2010-03-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] 化学プローブを用いた内因性ニトロ化ヌクレオチドの代謝研究2010

    • Author(s)
      斎藤洋平・伊藤千秋・澤智裕・赤池孝章・有本博一
    • Organizer
      日本化学会 第90春季年会
    • Place of Presentation
      近畿大学 本部キャンパス(大阪府東大阪市)
    • Year and Date
      2010-03-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] Chemical probes for elucidation of metabolism of nitrated nucleotides2010

    • Author(s)
      Y.Saito, C.Ito, T.Sawa, T.Akaike, H.Arimoto
    • Organizer
      Tetrahedron Symposium 2010
    • Place of Presentation
      中華人民共和国北京大学
    • Related Report
      2010 Self-evaluation Report
  • [Presentation] 内因性ニトロ化核酸の研究(5)2009

    • Author(s)
      斎藤洋平・藤井重元・澤智裕・赤池孝章・有本博一
    • Organizer
      日本化学会第89春季年会
    • Place of Presentation
      日本大学理工学部
    • Year and Date
      2009-03-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] 内因性ニトロ化核酸の研究(6)2009

    • Author(s)
      伊藤千秋・斎藤洋平・岡本竜哉・澤智裕・赤池孝章・有本博一
    • Organizer
      日本化学会第89春季年会
    • Place of Presentation
      日本大学理工学部
    • Year and Date
      2009-03-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] 内因性ニトロ化核酸の研究(7)2009

    • Author(s)
      田野井隆・木田恵里子・斎藤洋平・澤智裕・赤池孝章・有本博一
    • Organizer
      日本化学会第89春季年会
    • Place of Presentation
      日本大学理工学部
    • Year and Date
      2009-03-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] Chemical Approaches for Understanding and Controlling Infectious Diseases

    • Author(s)
      Hirokazu Arimoto
    • Organizer
      The Uehara Memorial Foundation Synposium-2011: Chembiomolecular Science: at the Frontier of Chemistry and Biology
    • Place of Presentation
      ハイアットリージェンシー東京
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] 化学プローブを駆使したニトロ化ヌクレオチドの動態解明

    • Author(s)
      有本博一
    • Organizer
      第84回 日本生化学会大会 シンポジウム「活性酸素種の可視化と情報伝達系解明への応用」
    • Place of Presentation
      京都国際会館
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] 感染症の制御に向けた化学からのアプローチ

    • Author(s)
      有本博一
    • Organizer
      中西シンポジウム2012
    • Place of Presentation
      慶応義塾大学
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Remarks]

    • URL

      http://www.agri.tohoku.ac.jp/bunseki/ArimotoGroup.html

    • Related Report
      2013 Final Research Report
  • [Remarks] ① Molecular Cell(論文掲載誌)2013年12月26日号「8-Nitro-cGMP -A New Player in Antibacterial Autophagy」 報道等(計5件)

    • Related Report
      2013 Final Research Report
  • [Remarks] ②科学新聞 2013年12月6日 「細菌を細胞から排除:東北大など「鍵分子」発見」 報道等(計5件)

    • Related Report
      2013 Final Research Report
  • [Remarks] ③朝日新聞 2013年12月5日朝刊「細胞内で異物につく分子 東北大・東京医科歯科大が発見」 報道等(計5件)

    • Related Report
      2013 Final Research Report
  • [Remarks] ④ 毎日新聞 2013年11月28日朝刊「細胞の細菌排除メカニズムを解明」 報道等(計5件)

    • Related Report
      2013 Final Research Report
  • [Remarks] ⑤ 河北新報 2013年11月22日朝刊「細胞侵入細菌に結合 目印役の分子発見」 報道等(計5件)

    • Related Report
      2013 Final Research Report
  • [Remarks] 細胞から細菌を排除するための鍵分子を発見

    • URL

      http://www.tohoku.ac.jp/japanese/2013/11/press20131115-01.html

    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗8-ニトロサイクリックグアノシン3',5'-一リン酸抗体2011

    • Inventor(s)
      赤池孝章、有本博一、芥 照夫、佐々本一美
    • Industrial Property Rights Holder
      国立大学法人 熊本大学 、国立大学法人名古屋大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2011-11-11
    • Related Report
      2013 Final Research Report

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Published: 2008-04-01   Modified: 2019-07-29  

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