Regulation of glutathione production by sulfuration induced by polysulfide/hydrogen sulfide
Project/Area Number |
17K08613
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General pharmacology
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Research Institution | Tokyo University of Science, Yamaguchi (2019-2020) National Center of Neurology and Psychiatry (2017-2018) |
Principal Investigator |
Kimura Yuka 山陽小野田市立山口東京理科大学, 薬学部, 研究員 (60425692)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 硫化水素 / ポリサルファイド / MPST / 過硫化 / TRPA1 / 結合型硫黄 / ノックアウト / D-セリン / 統合失調症 / ノックアウトラット / 亜硫酸 / 酸化ストレス / グルタチオン / システイン / 生理活性 |
Outline of Final Research Achievements |
3-Mercaptopyruvate sulfurtransferase (MPST) biosynthesizes hydrogen sulfide (H2S) and polysulfides (H2Sn), which sulfurate (addition of sulfur) cysteine residues of proteins to increase amount of bound sulfane sulfur. We made clear that MPST is required to produce bound sulfane sulfur by using MPST knock out mice. In addition, we demonstrated that 1) MPST sulfurates endogenous cysteine or glutathione (GSH) to produce redox regulators, cysteine persulfide (Cys-SSH) or glutathione persulfide (GSSH), 2) Sulfite (H2SO3), an oxidative product of H2S and H2Sn, protects neuronal cells from oxidative stress, 3) H2Sn produced from interaction between H2S and nitric oxide (NO), activate TRPA1 channel to synergically induce calcium response.
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Academic Significance and Societal Importance of the Research Achievements |
H2S、H2Snはシグナル分子として確立してきたが、そのターゲットやシグナル経路については不明な点が多い。本研究からH2S、H2Snに加えて、Cys-SSH、GSSH、過硫化蛋白質などが生体内に存在し、シグナル分子としてレドックス制御に関わることがわかってきた。H2S、H2Snは不安定だが、その酸化物亜硫酸(H2SO3)に強力な酸化ストレス防御作用があることがわかり、H2S、H2Snの下流の分子が生物作用を担う可能性も見えてきた。この知見が既に始まっているH2S、H2Snの創薬に生かされことを期待する。
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Report
(5 results)
Research Products
(37 results)
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[Journal Article] Discovery and Mechanistic Characterization of Selective Inhibitors of H2S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide2017
Author(s)
K. Hanaoka, K. Sasakura, Y. Suwanai, S. Toma-Fukai, K. Shimamoto, Y. Takano, N. Shibuya, T. Terai, T. Komatsu, T. Ueno, Y. Ogasawara, Y. Tsuchiya, Y. Watanabe, H. Kimura, C. Wang, M. Uchiyama, H. Kojima, T. Okabe, Y. Urano, T. Shimizu, T. Nagano
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Journal Title
Sci. Rep.
Volume: 7
Issue: 1
Pages: 40227-40227
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Development of a Reversible Fluorescent Probe for Reactive Sulfur Species, Sulfane Sulfur, and its Biological Application2017
Author(s)
Takano Y, Hanaoka K, Shimamoto K, Miyamoto R, Komatsu T, Ueno T, Terai T, Kimura H, Nagano T, Urano Y
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Journal Title
Chem Commun
Volume: 53
Issue: 6
Pages: 1064-1067
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] 3-Mercaptopyruvate sulfurtransferase produces potential redox regularots cysteine- and glutathione-persulfide (Cys-SSH and GSSH) together with signaling molecules H2S2, H2S3 and H2S.2017
Author(s)
Kimura, Y., Koike, S., Shibuya, N., Lefer, D., Ogasawara, Y., Kimura, H.
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Journal Title
Sci. Rep.
Volume: 7
Issue: 1
Pages: 10459-10459
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Analysis of endogenous H2S and H2Sn in mouse brain by high-performance liquid chromatography with fluorescence and tandem mass spectrometric detection.2017
Author(s)
Koike, S., Kawamura, K., Kimura, Y., Shibuya, N., Kimura, H., Ogasawara, Y.
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Journal Title
Free Rad. Biol. Med.
Volume: 113
Pages: 355-362
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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