Elucidation of the activation mechanism of TRPA1 channel by hydrogen sulfide-derived polysulfide

2017 Fiscal Year Final Research Report

• Project/Area Number: 26460352
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• 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)
• Project Period (FY): 2014-04-01 – 2018-03-31
• 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

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.

Free Research Field

神経科学、薬理学