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Study on a second messenger, 8-mercapt-cGMP, of hydrogen sulfide in nervous system

Research Project

Project/Area Number 25430069
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionOsaka Prefecture University

Principal Investigator

Ihara Hideshi  大阪府立大学, 理学(系)研究科(研究院), 准教授 (60254447)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords8-メルカプト-cGMP / 8-ニトロ-cGMP / システインパーサルファイド / 活性イオウ分子 / メチル水銀 / レドックスシグナル / 8-二トロ-cGMP / 活性イオウ分子種 / 一酸化窒素/活性酸素シグナル / NO/ROSシグナル / 硫化水素 / 活性イオウ
Outline of Final Research Achievements

It is found that reactive persulfides and polysulfides are formed endogenously from both small molecule species and proteins in high amounts in mammalian cells and tissues. Quantitation of these species indicates that high concentrations of glutathione persulfide (perhydropersulfide >100 μM) and other cysteine persulfide and polysulfide derivatives in peptides/proteins were endogenously produced and maintained in the plasma, cells, and tissues of mammals (rodent and human). It is expected that persulfides are especially nucleophilic and reducing. This view was found to be the case, because they quickly react with H2O2 and a recently described biologically generated electrophile 8-nitro-cGMP to form 8-mercapt-cGMP. Indeed, 8-mercapt-cGMP formation in nervous system was confirmed by LC-MSMS and immunocytochemistry. Furthermore, a novel mechanism of methylmercury-induced cytotoxicity, that is disruption of redox signaling regulated reactive sulfur species, was also revealed.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (29 results)

All 2016 2015 2014 2013

All Journal Article (12 results) (of which Peer Reviewed: 10 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) (of which Invited: 4 results) Book (1 results)

  • [Journal Article] Redox signaling regulated by electrophiles and reactive sulfur species2016

    • Author(s)
      Nishida M, Kumagai Y, Ihara H, Fujii S, Motohashi H, Akaike T.
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 58 Issue: 2 Pages: 91-98

    • DOI

      10.3164/jcbn.15-111

    • NAID

      130005132519

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Formation of Sulfur Adducts of N-Acetyl-p-benzoquinoneimine, an Electrophilic Metabolite of Acetaminophen in Vivo: Participation of Reactive Persulfides.2015

    • Author(s)
      Abiko Y., Ishii I., Kamata S., Tsuchiya Y., Watanabe Y., Ihara H., Akaike T., Kumagai Y.
    • Journal Title

      Chem. Res. Toxicol.

      Volume: 28 Issue: 9 Pages: 1796-1802

    • DOI

      10.1021/acs.chemrestox.5b00245

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 8-Nitro-cGMP Enhances SNARE Complex Formation through S-Guanylation of Cys90 in SNAP252015

    • Author(s)
      K. Kunieda, H. Tsutsuki, T. Ida, Y. Kishimoto, S. Kasamatsu, T. Sawa, N. Goshima, M. Itakura, M. Takahashi, T. Akaike, H. Ihara
    • Journal Title

      ACS Chemical Neuroscience

      Volume: 6 Issue: 10 Pages: 1715-1725

    • DOI

      10.1021/acschemneuro.5b00196

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 8-Mercapto-cyclic GMP mediates hydrogen sulfide-induced stomatal closure in Arabidopsis.2015

    • Author(s)
      Honda K, Yamada N, Yoshida R, Ihara H, Sawa T, Akaike T, Iwai S.
    • Journal Title

      Plant Cell Physiol.

      Volume: 56 Issue: 8 Pages: 1481-1489

    • DOI

      10.1093/pcp/pcv069

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nuclear-translocated Glyceraldehyde-3-phosphate Dehydrogenase Promotes Poly(ADP-ribose) Polymerase-1 Activation during Oxidative/Nitrosative Stress in Stroke.2015

    • Author(s)
      Nakajima H, Kubo T, Ihara H, Hikida T, Danjo T, Nakatsuji M, Shahani N, Itakura M, Ono Y, Azuma YT, Inui T, Kamiya A, Sawa A, Takeuchi T.
    • Journal Title

      J. Biol. Chem.

      Volume: 290 Pages: 14493-14503

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RSSの生体内検出とイメージング2015

    • Author(s)
      居原 秀、大内雄也
    • Journal Title

      細胞工学

      Volume: 34 Pages: 397-401

    • Related Report
      2014 Research-status Report
  • [Journal Article] Redox signal regulation via nNOS phosphorylation at Ser847 in PC12 cells and rat cerebellar granule neurons.2014

    • Author(s)
      Kasamats S, Watanabe Y, Sawa T, Akaike T, Ihara H.
    • Journal Title

      Biochem. J.

      Volume: 459 Issue: 2 Pages: 251-263

    • DOI

      10.1042/bj20131262

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling.2014

    • Author(s)
      Ida T, Sawa T, Ihara H, Tsucr iya Y, Watanabe Y, Kumagai Y, Suematsu M, Motohashi H, Fujii S. Matsunaga T, Yamamoto M, Ono K, Devarie-Baez N O, Xian M, Fukuto J M, Akaike T.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: (印刷中) Issue: 21 Pages: 7606-7611

    • DOI

      10.1073/pnas.1321232111

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Theophylline potentiates lipopolysaccharide-induced NO production in cultured astrocytes.2014

    • Author(s)
      Ogawa M, Takano K, Kawabe K, Moriyama M, Ihara H, Nakamura Y.
    • Journal Title

      Neurochem Res.

      Volume: 39 Pages: 107-16

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Formation, signaling functions, and metabolisms of nitrated cyclic nucleotide.2013

    • Author(s)
      Sawa T, Ihara H, Ida T, Fujii S, Nishida M and Akaike T.
    • Journal Title

      Nitric Oxide

      Volume: 34 Pages: 10-18

    • DOI

      10.1016/j.niox.2013.04.004

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nitric oxide enhances increase in cytosolic Ca(2+) and promotes nicotine-triggered MAPK pathway in PC12 cells.2013

    • Author(s)
      Kajiwara A, Tsuchiya Y, Takata T, Nyunoya M, Nozaki N, Ihara H, Watanabe Y.
    • Journal Title

      Nitric Oxide.

      Volume: 34 Pages: 3-9

    • DOI

      10.1016/j.niox.2013.04.002

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] レドックスメタボロミクス2013

    • Author(s)
      居原 秀
    • Journal Title

      医学のあゆみ

      Volume: 247 Pages: 832-838

    • Related Report
      2013 Research-status Report
  • [Presentation] 活性イオウシグナルの分子基盤2016

    • Author(s)
      居原 秀
    • Organizer
      第32回臨床フリーラジカル会議
    • Place of Presentation
      けぶりかわ(京都府亀岡市)
    • Year and Date
      2016-01-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 活性イオウ分子のレドクスシグナル制御異常によるメチル水銀毒性の発現機構2015

    • Author(s)
      居原 秀
    • Organizer
      第42回日本毒性学会
    • Place of Presentation
      金沢市アートホール(石川県金沢市)
    • Year and Date
      2015-06-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 有機水銀の新規毒性発現機構:活性イオウ分子によるNO/ROSレドクスシグナル制御の破綻2015

    • Author(s)
      居原 秀
    • Organizer
      第88回日本薬理学会
    • Place of Presentation
      名古屋国際会議場(愛知県 名古屋市)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 有機水銀の新規毒性発現機構:活性イオウ分子のNO/ROSレドクスシグナル制御異常2014

    • Author(s)
      居原 秀
    • Organizer
      フォーラム2014:衛生薬学・環境トキシコロジー
    • Place of Presentation
      つくば国際会議場(茨城県 つくば市)
    • Year and Date
      2014-09-19 – 2014-09-20
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Redox signal regulation via nNOS phosphorylation at Ser847 in PC12 cells and rat cerebellar granule neurons2014

    • Author(s)
      Ihara H, Kasamatsu S, Watanabe Y, Sawa T, Akaike T
    • Organizer
      第8回国際NO学会学術集会
    • Place of Presentation
      Cleveland、USA
    • Year and Date
      2014-06-16 – 2014-06-20
    • Related Report
      2014 Research-status Report
  • [Presentation] Metabolism of 8-nitro-cGMP and regulation of electrophilic signaling by reactive sulfur species2014

    • Author(s)
      Ida T, Sawa T, Ihara H, Tsuchiya Y, Watanabe Y, Kumagai Y, Motohashi H, Fujii S, Matsunaga T, Yamamoto M, Ono K, Fukuto J, Akaike T
    • Organizer
      第8回国際NO学会学術集会
    • Place of Presentation
      Cleveland、USA
    • Year and Date
      2014-06-16 – 2014-06-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 活性システインパーサルファイドとS-ポリチオレーションが酸化ストレスとレドックスシグナルを制御する2014

    • Author(s)
      井田 智章, 澤 智裕, 居原 秀, 土屋 幸弘, 松永 哲郎, 藤井重元, 熊谷 嘉人, 渡邊 泰男, Fukuto Jon, 赤池 孝章
    • Organizer
      第14回日本NO学会学術集会
    • Place of Presentation
      ニューオータニ佐賀(佐賀県 佐賀市)
    • Year and Date
      2014-05-16 – 2014-05-17
    • Related Report
      2014 Research-status Report
  • [Presentation] nNOSのSer847リン酸化を介したNO/ROSレドックスシグナル制御2014

    • Author(s)
      笠松 真吾, 渡邊 泰男, 澤 智裕, 赤池 孝章, 居原 秀
    • Organizer
      第14回日本NO学会学術集会
    • Place of Presentation
      ニューオータニ佐賀(佐賀県 佐賀市)
    • Year and Date
      2014-05-16 – 2014-05-17
    • Related Report
      2014 Research-status Report
  • [Presentation] 有機水銀の新規毒性発現機構:活性イオウ分子種のNO/ROSシグナル制御異常2014

    • Author(s)
      石崎健勝, 飯田聡史, 笠松真吾, 津々木博康, 中野長久, 赤池孝章, 居原 秀
    • Organizer
      第14回日本NO学会学術集会
    • Place of Presentation
      ニューオータニ佐賀(佐賀県 佐賀市)
    • Year and Date
      2014-05-16 – 2014-05-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Superoxide Generation from Neuronal Nitric Oxide Synthase and its Involvement in the Regulation of Nitric Oxide/Reactive Oxygen Species Signaling2014

    • Author(s)
      Hiroyasu Tsutsuki, Shingo Kasamatsu, Tomoaki Ida, Tomohiro Sawa , Takaaki Akaike, Hideshi Ihara
    • Organizer
      SFRRI2014
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] Synaptosomal-associated protein 25(SNAP25)のS-guanyl化によるSNARE複合体形成の調節2013

    • Author(s)
      居原秀、國枝恒兵、井田智章、澤智裕、赤池孝章
    • Organizer
      第13回日本NO学会学術集会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Research-status Report
  • [Presentation] 生体内システインパースルフィドの生成動態とその生理機能の解析2013

    • Author(s)
      井田 智章, 澤 智裕, 土屋 幸弘, 小野 勝彦, 藤井 重元, 渡邉 泰男, 居原 秀, 赤池 孝章
    • Organizer
      第13回日本NO学会学術集会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Research-status Report
  • [Presentation] NOによるp38MAPKリン酸化シグナルの増強とそのカルシウムの関与2013

    • Author(s)
      土屋幸宏、梶原綾、丹生谷真弓、居原秀、渡邊泰男
    • Organizer
      第13回日本NO学会学術集会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Research-status Report
  • [Presentation] 小脳顆粒神経細胞におけるニコチンの神経保護効果: nNOSリン酸化によるNO/ROSシグナル制御の関与2013

    • Author(s)
      笠松 真吾, 渡邊 泰男, 澤 智裕, 赤池 孝章, 居原 秀
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 新規レドックス制御因子:過イオウ化システイン誘導体のメタボローム解析2013

    • Author(s)
      井田 智章, 澤 智裕, 土屋 幸弘, 小野 勝彦, 藤井 重元, 渡邉 泰男, 居原 秀, 赤池 孝章
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 有機水銀の新規毒性発現機構: 活性イオウ分子の新電子シグナル制御異常2013

    • Author(s)
      笠松真吾、澤智裕、赤池孝章、居原秀
    • Organizer
      第30回臨床フリーラジカル会議
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Book] 実験医学別冊「細胞の酸化ストレスを量る」2013

    • Author(s)
      澤智裕、居原秀、赤池孝章
    • Total Pages
      10
    • Publisher
      羊土社
    • Related Report
      2013 Research-status Report

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

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