Hydrogen peroxide is the major oxidant product of xanthine oxidase.
Hydrogen peroxide is the major oxidant product of xanthine oxidase.
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DOI：
10.1016/j.freeradbiomed.2009.11.012
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发表时间：
2010-02-15
影响因子：
7.4
通讯作者：
Tarpey, Margaret M.
中科院分区：
文献类型：
--
作者：
Kelley, Eric E.;Khoo, Nicholas K. H.;Hundley, Nicholas J.;Malik, Umair Z.;Freeman, Bruce A.;Tarpey, Margaret M.
Xanthine oxidase (XO) is a critical source of reactive oxygen species (ROS) in inflammatory disease.然而，焦点几乎完全集中在 XO 衍生的超氧化物 (O2•−) 上，而从 XO 直接生产 H2O2 的研究较少。 Therefore, we examined the relative quantities of O2•− and H2O2 produced by XO under a range (1–21%) of O2 tensions. At O2 concentrations between 10 and 21 %, H2O2 accounted for ~ 75% of ROS production.随着 O2 浓度降低，H2O2 的形成呈浓度依赖性增加，占 1% O2 时 ROS 产生的 90%。 Alterations in pH between 5.5 and 7.4 did not affect the relative proportions of H2O2 and O2•− formation.通过与肝素-琼脂糖结合，固定 XO，在常氧和缺氧条件下，相对 H2O2 产量进一步提高了约 30%。此外，与牛主动脉内皮细胞顶端表面的糖胺聚糖（GAG）结合的 XO 表现出类似的 ROS 产生特征。这些数据表明，H2O2 是 XO 在临床相关条件下产生的主要反应产物（70-95%），并强调了在检查 XO 催化的 ROS 在炎症过程和细胞信号传导中的贡献作用时，H2O2 作为关键因素的重要性。
Xanthine oxidase (XO) is a critical source of reactive oxygen species (ROS) in inflammatory disease. Focus, however, has centered almost exclusively on XO-derived superoxide (O2•−) while direct H2O2 production from XO has been less well-investigated. Therefore, we examined the relative quantities of O2•− and H2O2 produced by XO under a range (1–21%) of O2 tensions. At O2 concentrations between 10 and 21 %, H2O2 accounted for ~ 75% of ROS production. As O2 concentrations were lowered, there was a concentration-dependent increase in H2O2 formation, accounting for 90% of ROS production at 1% O2. Alterations in pH between 5.5 and 7.4 did not affect the relative proportions of H2O2 and O2•− formation. Immobilization of XO, by binding to heparin-Sepharose, further enhanced relative H2O2 production by ~30%, under both normoxic and hypoxic conditions. Furthermore, XO bound to glycosaminoglycans (GAGs) on the apical surface of bovine aortic endothelial cells demonstrated a similar ROS production profile. These data establish H2O2 as the dominant (70–95%) reactive product produced by XO under clinically relevant conditions and emphasize the importance of H2O2 as a critical factor when examining the contributory roles of XO-catalyzed ROS in inflammatory processes as well as cellular signaling.
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通讯作者：
Bondjers, G
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