Molecular toxicological study on the species differences in activation of nociceptive TRPA1 channel
| Project/Area Number |
18K06641
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Meijo University |
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Principal Investigator |
Jinno Hideto 名城大学, 薬学部, 教授 (10179096)
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| Co-Investigator(Kenkyū-buntansha) |
香川 聡子 横浜薬科大学, 薬学部, 教授 (40188313)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 侵害刺激 / TRPA1 / 種差 / ケイ皮酸エステル類 / 侵害受容体 / フェルラ酸エステル類 / TRPチャネル / ゲノム編集 / 消化管ホルモン |
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| Outline of Final Research Achievements |
In this study, we established a mutant TRPA1 in which three reactive cysteines (C621, C641 and C665) are substituted for serine resides, and chimeric TRPA1s in which four segments (N-terminal, membrane-penetrating regions 1-4 and 5-6, and the C-terminal) are replaced with each other between human and mouse. By using these mutant TRPA1s, we examined the TRPA1 activation by a group of cinnamate derivatives, and found that some cinnamate derivatives with the species differences of ~4 times elicited a mixed-type of activation mechanisms, or activation by covalent-binding with reactive cysteine residues and ligand binding with transmembrane regions 1-4.
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| Academic Significance and Societal Importance of the Research Achievements |
TRPA1は寒冷刺激の他に、さまざまな化学物質によって活性化される侵害受容体である。一般に、化学物質の安全性は主にげっ歯類を用いる動物実験によって評価され、安全係数の導入によってヒトに外挿されることを考慮すると、両者の間の種差は、リスク評価の妥当性に影響を及ぼす重要な因子であるといえる。本研究で得られた知見は、TRPA1が関与する生体影響に関して、げっ歯類モデルを用いるリスク評価に限界があることを示している。
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Report
(4 results)
Research Products
(11 results)
