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シングレット分子酸素は,炎症における血管調子と血圧を調節する
Christopher P Stanley1, Ghassan J Maghzal1,2, Anita Ayer1,2
1Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
Nature
|February 15, 2019
まとめ
哺乳類のインドレアミン2,3-二酸化酵素1はシングレット酸素 (1O2) とトリプトファン由来水酸化物を生成し,炎症下で血圧と動脈トーンを調節するシグナル分子の役割を果たします.
科学分野:
- 生物化学
- 生理学
- 分子生物学
背景:
- シングレット分子酸素 (1O2) は植物,細菌,真菌では知られているが,哺乳類にはない.
- インドレアミン2,3-二酸化酵素1 (IDO1) はトリプトファンの代謝に関与し,炎症時に動脈内皮細胞で発現する酵素である.
- IDO1による1O2生成の役割と,哺乳類における血圧調節への貢献は,以前は知られていなかった.
研究 の 目的:
- 動脈の IDO1 が 1O2 を生成するかどうかを調べる.
- IDO1によって生成される 1O2 が血圧制御に影響するかどうかを判断する.
- IDO1による血圧調節のメカニズムを解明する.
主な方法:
- IDO1による1O2生成を,過酸化水素の存在で検出するための酵素分析.
- L-トリプトファンの三環水酸化物へのステレオ選択的酸化.
- トリプトファン製の水酸化物の血圧と血管トーンに対する影響を評価するインビボ試験.
- 信号伝達経路におけるタンパク質キナーゼG1αのCys42の役割を調査する.
主要な成果:
- 動脈のIDO1は,過酸化水素の存在で1O2を生成する.
- IDO1は,L-トリプトファンの三環水酸化物へのステレオ選択的酸化を触媒化する.
- トリプトファン由来ヒドロペロキシドは,内生的なシグナル分子としてin vivoで機能する.
- この水酸化物は,タンパク質キナーゼG1αに依存して,動脈のリラックスを引き起こし,血圧を下げる.
- ダイオキシゲネーゼの新種の酸化活性化が確認された.
結論:
- 哺乳類のIDO1は1O2と独特のアミノ酸由来ヒドロペロキシドを生成する.
- このメカニズムは,哺乳類における1O2の病理学的役割を確立する.
- 血管のトーンと血圧を 調節する新しい経路が 発見されました
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