ニトロキシドは,モデルシステムと細胞内のミエロペロキシダースによって触媒化されたチールラジカルを除去する
Grigory G Borisenko1, Ian Martin, Qing Zhao
1Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. grigoryb@yahoo.com
Journal of the American Chemical Society
|July 30, 2004
まとめ
酸化窒素のラジカルは有害なグルタチオニルラジカル (GS(*)) と反応して,二次アミンを形成し,以前は未知の経路である. この相互作用は,グルタチオン (GSH) を保存し,フリーラジカルを取り除き,細胞を保護します.
科学分野:
- バイオケミストリー バイオケミストリー
- フリーラジカルの化学
- 細胞生物学 細胞生物学
背景:
- 酸化窒素のラジカルは,生物学的システム内の反応性ラジカルを除去する抗酸化物質として知られています.
- グルタチオン (GSH) は主要な細胞内抗酸化物質ですが,その過激な形態 (GS(*)) は有害である可能性があります.
- 窒素酸化物,GS,およびチオールとの相互作用,および細胞における窒素酸化物の代謝は十分に理解されていません.
研究 の 目的:
- ニトロキシードラジカルとグルタチオニルラジカル (GS) の相互作用を調査する.
- 細胞内の窒素酸化物の代謝経路,特に二次アミンへの変換を解明する.
- 生きている細胞における窒素酸化物の抗酸化メカニズムを特徴づける.
主な方法:
- GSを検出するためにAc-Tempo (光アクリジン-窒素酸化物結合体) を使用した敏感な方法を開発しました.
- 電子パラマグネティック共振 (EPR) スペクトロスコピーを利用し,窒素酸化物信号の衰えを監視しました.
- 高性能液体染色法 (HPLC) と質量スペクトロメトリを用いて,反応産物を特定する.
- H(2) O(2) とフェノールで刺激されたHL-60細胞の反応を研究した.
主要な成果:
- GS(*) 基は,二次アミンを形成するために,窒素酸化物と効率的かつ不可逆的に反応する.
- Ac-TempoのEPR信号は減少し,GSと反応したときにアクリジンの光が増加しました.
- HPLC-MS分析では,Ac-Tempoがアクリジン-ピペリジンに変換され,GSHが硫酸に酸化することが示されました.
- Ac-Tempoは,フェノール/GSの毒性から細胞を保護し,細胞内GSHを保存しています.
結論:
- 酸化窒素はGSと反応して二次アミンを形成し,新しい代謝経路を表します.
- Ac-Tempoは,GS(*) の相互作用を検出し,窒素酸化物-GS(*) の相互作用を特徴付けるのに有効な探査機として機能します.
- ニトロキシドは,GS(*) スキャビングとGSH保存を含む新しいメカニズムを通じて抗酸化活性を示します.
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