Elucidation of the activation mechanism of TRPA1 channel by hydrogen sulfide-derived polysulfide
Project/Area Number |
26460352
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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 | National Center of Neurology and Psychiatry |
Principal Investigator |
Kimura Yuka 国立研究開発法人国立精神・神経医療研究センター, 神経研究所, 科研費研究員 (60425692)
|
Co-Investigator(Renkei-kenkyūsha) |
KIMURA Hideo 国立精神, 神経医療研究センター, 研究員 (30321889)
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Project Period (FY) |
2014-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | ポリサルファイド / 硫化水素 / TRPA1 / 3-メルカプトピルビン酸イオウ転移酵素 / シグナル分子 / メルカプトピルビン酸 / 脳 / レドックス調節 / 3-メルカプトピルビン酸硫黄転移酵素 / 酵素的産生 / ロダネース / 3メルカプトピルビン酸硫黄転移酵素 / Rhodanese / 細胞内カルシウム / アストロサイト / シグナリング |
Outline of Final Research Achievements |
We demonstrated that hydrogen sulfide(H2S) and polysulfide (H2Sn、n≧2)are endogenous signaling molecules. In the present study, we have elucidated the mechanism of activation of transient receptor potential ankyrin1 (TRPA1) channels; 1) Sulfhydration of cysteine residues in TRPA1 by H2Sn and the subsequent formation of a disulfide bond, induce conformational change to activate the channels, 2) H2Sn is produced by 3-mercaptopyruvate sulfurtransferase, 3) H2Sn react with cysteine and glutathione to produce Cys-SSH and GSSH, potential regulators of cellular redox state.
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Report
(6 results)
Research Products
(74 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] 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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[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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[Presentation] マウスにおける生理活性物質H2Sの産生経路2016
Author(s)
渋谷典弘, 小池伸, 田中真紀子, 湯浅(石上)磨里, 木村由佳, 小笠原祐樹2, 福井清3, 永原則之, 木村英雄
Organizer
第89回日本薬理学会年会
Place of Presentation
パシフィコ横浜会議センター
Year and Date
2016-03-09
Related Report
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[Presentation] 生理活性物質硫化水素の産生経路2015
Author(s)
渋谷典弘, 小池伸, 田中真紀子, 湯浅(石上)磨里, 木村由佳, 小笠原祐樹, 福井清, 永原則之, 木村英雄
Organizer
BMB2015
Place of Presentation
神戸ポートアイランド
Year and Date
2015-12-01
Related Report
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[Presentation] The pharmacology of H2S2014
Author(s)
Hideo Kimura
Organizer
17th World Congress of basic and clinical Pharmacology
Place of Presentation
International Convention Center, Cape Town, South Africa
Year and Date
2014-07-13 – 2014-07-18
Related Report
Invited
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