Nitroso-redox status and vascular function in marginal and severe ascorbate deficiency.
Nitroso-redox status and vascular function in marginal and severe ascorbate deficiency.
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DOI：
10.1089/ars.2011.4201
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发表时间：
2012-08
影响因子：
6.6
通讯作者：
M. García-Saura;Fumito Saijo;N. Bryan;Selena M. Bauer;Juan Rodriguez;M. Feelisch
中科院分区：
文献类型：
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作者：
M. García-Saura;Fumito Saijo;N. Bryan;Selena M. Bauer;Juan Rodriguez;M. Feelisch
边缘性维生素C（抗坏血酸）缺乏是心血管疾病的一个普遍但未被充分认识的危险因素。抗坏血酸沿着谷胱甘肽在抗氧化防御和氧化还原信号传导中起重要作用。一氧化氮（NO）和活性氧的产生及其相互作用，引起亚硝基和亚硝酰基产物的形成，是氧化还原调节/信号网络的关键组成部分。许多体外研究表明，这些系统通过多种化学转化反应相互连接，但对其在体内的动力学和意义知之甚少。目的：研究不能合成维生素C的大鼠在抗坏血酸耗竭过程中NO/氧化还原状态和血管功能变化的时间过程。结果我们发现，在抗坏血酸缺乏的发展过程中，血液和重要器官中的氧化还原和蛋白质硝基化状态发生动态变化。长期边缘抗坏血酸缺乏症与抗坏血酸和谷胱甘肽氧化还原和NO状态的细胞/组织特异性扰动有关。坏血病的发展较早，在轻微缺乏充分补充的动物相比，与钝化补偿NO生产和分离的生化临床病理学在前者。奇怪的是，无论抗坏血酸状态如何，主动脉内皮反应性增强而不是受损。创新/结论：NO产生和蛋白质硝基化的增强是急性抗坏血酸剥夺的氧化还原应激的整体反应。边缘性抗坏血酸缺乏的心血管风险升高可能与NO/氧化还原敏感性信号节点的扰动有关，而与血管张力的调节无关。这种新模型可能对未来研究边缘抗坏血酸缺乏症中的氧化还原敏感事件有价值。
UNLABELLED Marginal vitamin C (ascorbic acid) deficiency is a prevalent yet underappreciated risk factor for cardiovascular disease. Along with glutathione, ascorbate plays important roles in antioxidant defense and redox signaling. Production of nitric oxide (NO) and reactive oxygen species and their interaction, giving rise to nitroso and nitrosyl product formation, are key components of the redox regulation/signaling network. Numerous in vitro studies have demonstrated that these systems are interconnected via multiple chemical transformation reactions, but little is known about their dynamics and significance in vivo. AIMS We sought to investigate the time-course of changes in NO/redox status and vascular function during ascorbate depletion in rats unable to synthesize vitamin C. RESULTS We here show that both redox and protein nitros(yl)ation status in blood and vital organs vary dynamically during development of ascorbate deficiency. Prolonged marginal ascorbate deficiency is associated with cell/tissue-specific perturbations in ascorbate and glutathione redox and NO status. Scurvy develops earlier in marginally deficient compared to adequately supplemented animals, with blunted compensatory NO production and a dissociation of biochemistry from clinical symptomology in the former. Paradoxically, aortic endothelial reactivity is enhanced rather than impaired, irrespective of ascorbate status. Innovation/Conclusion: Enhanced NO production and protein nitros(yl)ation are integral responses to the redox stress of acute ascorbate deprivation. The elevated cardiovascular risk in marginal ascorbate deficiency is likely to be associated with perturbations of NO/redox-sensitive signaling nodes unrelated to the regulation of vascular tone. This new model may have merit for the future study of redox-sensitive events in marginal ascorbate deficiency.