Physiological roles of hydrogen sulfide and polysulfide
Project/Area Number |
17K08331
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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 |
Pharmacology in pharmacy
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Research Institution | Tokyo University of Science, Yamaguchi (2019-2020) National Center of Neurology and Psychiatry (2017-2018) |
Principal Investigator |
KIMURA HIDEO 山陽小野田市立山口東京理科大学, 薬学部, 教授 (30321889)
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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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | 硫化水素 / ポリサルファイド / TRPA1チャネル / 神経伝達調節 / 過硫化 / 海馬長期増強 / 3MST / 統合失調症 / ノックアウトラット / 亜硫酸 / 神経保護作用 / 3MST / TRPA1 / 記憶 / 一酸化窒素 / 質量分析 / 蛍光プローブ / 阻害剤 / シグナル分子 / 酸化還元 |
Outline of Final Research Achievements |
3-Mercaptopyruvate sulfurtransferase (3MST) produces hydrogen sulfide (H2S) and polyfulfides (H2Sn). H2Sn S-sulfurate cysteine residues of the target proteins, while H2S S-sulfurates the oxidized cysteie residues such as Cys-SOH to generate Cys-SSH. It correlate well with the increase in the amount of bound sulfane sulfur. We elucidated that 3MST increases S-sulfurated proteins, namely the levels of bound sulfane sulfur by using 3MST knockout mice. We also showed that the two cysteine residues of TRPA1 channels are S-sulfurated to activate the channels.
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Academic Significance and Societal Importance of the Research Achievements |
これまで、硫化水素(H2S)とポリサルファイド(H2Sn)による標的タンパクの活性化機構についてはよくわかっていなかった。今回、これら分子の生合成酵素である3-メルカプトピルビン酸イオウ転移酵素(3MST)ノックアウトマウスを使い、標的分子としては、TRPA1チャネルに注目して、その活性機構を明らかにした。本チャネルは血圧調節や記憶に関わるチャネルで、本研究によって、H2SやH2Snを放出する分子の開発によって血圧や記憶の改善に寄与する薬物の創生が期待される。
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Report
(5 results)
Research Products
(44 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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