Clarification of the endogenous formation of the novel cyclic nucleotide 8-SH-cGMP and its signaling function
Project/Area Number |
25870549
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Chemical biology
General medical chemistry
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Research Institution | Tohoku University |
Principal Investigator |
IDA Tomoaki 東北大学, 医学(系)研究科(研究院), 助教 (70570406)
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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Keywords | 8-SH-cGMP / 8-ニトロ-cGMP / 活性イオウ分子種 / S-S-グアニル化 / S-ポリチオール化タンパク質 / タンパク質翻訳後修飾 / 酸化ストレス / システインパースルフィド / タンパク質S-ポリチオール化 / レドックスシグナル / 活性酸素 / 一酸化窒素 / 8-Nitro-cGMP / ポリサルファ |
Outline of Final Research Achievements |
The cyclic nucleotide 8-SH-cGMP is produced by the metabolism of 8-nitro-cGMP, which serves as a secondary messenger for NO and reactive oxygen species signaling. However, the mechanisms controlling the formation and levels of intracellular 8-SH-cGMP have not yet been identified. In this study, the principal investigator precisely quantified the formation of 8-SH-GMP via a mass spectrometry-based metabolomic method. The results revealed that 8-SH-cGMP is produced from 8-nitro-cGMP via sulfhydration by reactive sulfur species generated from the cystathione beta-synthase and cystathionine gamma-lyase systems. Moreover, the formation of S-S-guanylation (cGMP adduction to the thiol group of the protein via disulfide linkage) was specifically identified using proteome analysis of S-polythiolation.
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Report
(3 results)
Research Products
(25 results)
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[Journal Article] Reactive sulfur species-mediated activation of the Keap1-Nrf2 pathway by 1,2-napthoquinone through sulfenic acids formation under oxidative stress.2015
Author(s)
Shinkai Y, Abiko Y, Ida T, Miura T, Kakehashi H, Ishii I, Nishida M, Sawa T, Akaike T, Kumagai Y.
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Journal Title
Chem Res Toxicol.
Volume: 印刷中
Issue: 5
Pages: 838-847
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Hyperhomocysteinemia abrogates fasting-induced cardioprotection against ischemia/reperfusion by limiting bioavailability of hydrogen sulfide anions.2015
Author(s)
Nakano S, Ishii I, Shinmura K, Tamaki K, Hishiki T, Akahoshi N, Ida T, Nakanishi T, Kamata S, Kumagai Y, Akaike T, Fukuda K, Sano M, Suematsu M.
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Journal Title
J Mol Med (Berl).
Volume: 印刷中
Issue: 8
Pages: 879-889
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Proc. Natl. Acad. Sci. USA
Volume: (印刷中)
Issue: 21
Pages: 7606-7611
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Promotion of atherosclerosis by Helicobacter cinaedi infection that involves macrophage-driven proinflammatory responses.2014
Author(s)
Khan S, Rahman H N A, Okamoto T, Matsunaga T, Fujiwara Y, Sawa T, Yoshitake J, Ono K, Ahmed K A, Rahaman M d M, Oyama K, Takeya M, Ida T, Kitamura Y, Fujii S, Akaike T.
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Journal Title
Sci. Rep.
Volume: (印刷中)
Issue: 1
Pages: 4680-4680
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] Metabolism of 8-nitro-cGMP and regulation of electrophilic signaling by reactive sulfur species2014
Author(s)
Tomoaki Ida, Tomohiro Sawa, Hideshi Ihara, Yukihiro Tsuchiya, Yasuo Watanabe, Yoshito Kumagai, Hozumi Motohashi, Shigemoto Fujii, Tetsuro Matsunaga, Masayuki Yamamoto, Katsuhiko Ono, Jon M. Fukuto, Takaaki Akaike
Organizer
Nitric Oxide-Nitrite/Nitrate Conference
Place of Presentation
Cleaveland, Ohio, USA
Year and Date
2014-06-16 – 2014-06-20
Related Report
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