University of Pittsburgh, Department of Anesthesiology and Vascular Medicine Institute, United States.
Nitric Oxide. 2013 Nov 1;34:19-26. doi: 10.1016/j.niox.2013.02.081. Epub 2013 Feb 27.
Numerous inflammatory disorders are associated with elevated levels of xanthine oxidoreductase (XOR) and allied enhancement of reactive species formation contributory to systemic pathology. Despite a long standing association between increased XOR activity and negative clinical outcomes, recent reports describe a paradigm shift where XOR mediates beneficial actions by catalyzing the reduction of NO2(-) to NO. While provocative, these observations contradict reports of improved outcomes in similar models upon XOR inhibition as well as reports revealing strict anoxia as a requisite for XOR-mediated NO formation. To garner a more clear understanding of conditions necessary for in vivo XOR-catalyzed NO production, this review critically analyzes the impact of O2 tension, pH, substrate concentrations, glycoaminoglycan docking and inhibition strategies on the nitrite reductase activity of XOR and reveals a hypoxic milieu where this process may be operative. As such, information herein serves to link recent reports in which XOR activity has been identified as mediating the beneficial outcomes resulting from nitrite supplementation to a microenvironmental setting where XOR can serve as substantial source of NO.
许多炎症性疾病与黄嘌呤氧化还原酶 (XOR) 水平升高有关，并且与之相关的活性氧形成的增强会导致全身病理。尽管 XOR 活性增加与负面临床结果之间存在长期关联，但最近的报告描述了一种范式转变，其中 XOR 通过催化 NO2(-) 还原为 NO 来介导有益作用。虽然这些观察结果令人振奋，但它们与 XOR 抑制后类似模型中改善结果的报告以及揭示严格缺氧是 XOR 介导的 NO 形成所必需的报告相矛盾。为了更清楚地了解体内 XOR 催化的 NO 产生所需的条件，本综述批判性地分析了 O2 张力、pH 值、底物浓度、糖胺聚糖对接和抑制策略对 XOR 的亚硝酸盐还原酶活性的影响，并揭示了缺氧环境，在此环境中，这一过程可能起作用。因此，本文提供的信息将最近的报告联系起来，这些报告表明 XOR 活性可介导硝酸盐补充带来的有益结果，并将其与 XOR 可作为大量 NO 来源的微环境联系起来。
