Hypoxia, especially altitude associated hypoxia is known to cause severe physiological alterations and life-threatening conditions. Impaired redox balance along with oxidative stress, protein carbonylation and instigation of apoptotic events are common sub-cellular events that follow the hypoxic insult. The role of nitric oxide (NO) is very dynamic and versatile in preventing the ill effects of hypoxia vis-a-vis reacting with oxidative species and causing protein nitrosylation. Although several mechanisms of NO-mediated cytoprotection are known during hypoxic insult, limited evidences are available to support the relationship between two downstream events of oxidative stress, protein carbonylation (caused by carbonyl; CO radical) and protein nitrosylation/nitration (caused by NO/peroxynitrite; ONOO radical). In this study, we investigated an entirely new aspect of NO protection in hypoxia involving cross talk between carbonylation and nitrosylation. Using standard NO inhibitor l-NAME and simulated hypoxic conditions in hypoxia-sensitive cell line H9c2, we evaluated the levels of radicals, cell death, mitochondrial membrane potential, levels of protein nitrosylation, protein nitration and carbonylation and glutathione content. The results were then carefully analyzed in light of NO bioavailability. Our study shows that reducing NO during hypoxia caused cell death via increased degree of carbonylation in proteins. This provides a new aspect of NO benefits which furthers opens new possibilities to explore potential mechanisms and effects of cross-talk between nitrosylation, protein nitration and carbonylation, especially through some common antioxidant mediators such as glutathione and thioredoxin.

缺氧，尤其是与海拔相关的缺氧会导致严重的生理变化和危及生命的状况。氧化还原平衡受损以及氧化应激，蛋白质羰基化和凋亡事件的诱因是缺氧损伤后常见的亚细胞事件。一氧化氮（NO）的作用是非常有活力和灵活的在防止缺氧的不良影响面对面的人与氧化物质发生反应，导致蛋白质亚硝化。尽管在缺氧性损伤过程中已知几种NO介导的细胞保护机制，但有限​​的证据支持氧化应激的两个下游事件，蛋白质羰基化（由羰基； CO自由基引起）和蛋白质亚硝基化/硝化（由NO /引起）之间的关系。过氧亚硝酸盐； ONOO自由基）。在这项研究中，我们研究了缺氧中NO保护的一个全新方面，涉及羰基化和亚硝基化之间的串扰。使用标准的NO抑制剂l-NAME和模拟缺氧条件下的缺氧敏感细胞株H9c2，我们评估了自由基的水平，细胞死亡，线粒体膜电位，蛋白质亚硝化水平，蛋白质硝化和羰基化水平以及谷胱甘肽含量。然后根据NO生物利用度仔细分析结果。我们的研究表明，在缺氧状态下减少NO会通过蛋白质中羰基化程度的提高而导致细胞死亡。这提供了NO益处的新方面，这进一步为探索亚硝化，蛋白质硝化和羰基化之间的串扰的潜在机制和效应提供了新的可能性，尤其是通过一些常见的抗氧化剂介质（例如谷胱甘肽和硫氧还蛋白）。