氧化物在模型系统和细胞中清除由髓氧化酶催化的基
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
概括
氧化基与有害的谷氨基基 (GS(*)) 反应形成二次氨基,这是以前未知的途径. 这种相互作用通过保存谷氨 (GSH) 和清除自由基来保护细胞.
科学领域:
- 生物化学 生物化学
- 自由基化学 自由基化学
- 细胞生物学 细胞生物学
背景情况:
- 氧化物基是已知的抗氧化剂,可以在生物系统中清除反应性基.
- 谷氨酸 (GSH) 是主要的细胞内抗氧化剂,但其激进形式 (GS(*)) 可能是有害的.
- 氧化物,GS(*) 和硫醇之间的相互作用,以及细胞中的氧化物代谢,尚不清楚.
研究的目的:
- 研究氧化物基和谷氨基基 (GS) 之间的相互作用.
- 阐明细胞内的氧化物代谢途径,特别是它们转化为二次胺.
- 描述活细胞中氧化物的抗氧化机制.
主要方法:
- 开发了一种使用Ac-Tempo (光亚克里丁-氧化物合物) 来检测GS的敏感方法.
- 使用电子磁共振 (EPR) 光谱来监测氧化信号衰变.
- 采用高性能液体染色学 (HPLC) 和质谱法来识别反应产物.
- 研究了HL-60细胞的反应,这些细胞被H(2) O(2) 和刺激.
主要成果:
- GS(*) 基因与氧化物有效且不可逆转地反应,形成二次氨基.
- 在与GS反应时,Ac-Tempo的EPR信号下降了,而阿克里丁光增加了.
- 在HPLC-MS分析中,Ac-Tempo转化为阿克里丁-皮佩里丁,GSH氧化为硫酸.
- 通过Ac-Tempo保护细胞免受/GS的毒性,并保存细胞内GSH.
结论:
- 氧化物与GS反应,形成二次胺,代表了一种新的代谢途径.
- Ac-Tempo 作为一种有效的探测器,用于检测GS(*) 和表征氧化物-GS(*) 相互作用.
- 氧化物通过一种新的机制表现出抗氧化活性,涉及GS(*) 清理和GSH保存.
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