Proteomic method identifies proteins nitrated in vivo during inflammatory challenge
Proteomic method identifies proteins nitrated in vivo during inflammatory challenge
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DOI：
10.1073/pnas.221269198
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发表时间：
2001-10-09
影响因子：
11.1
通讯作者：
Stuehr, DJ
中科院分区：
文献类型：
--
作者：
Aulak, KS;Miyagi, M;Stuehr, DJ
哮喘、败血症、移植排斥和许多神经退行性疾病中的炎症将NO合成的上调与酪氨酸处蛋白质硝化的增加相关联。硝化可导致蛋白质功能障碍，并参与发病机制，但很少有蛋白质，似乎在体内硝化已被确定。为了了解这种修饰如何影响生理学和疾病，我们在体内和细胞培养炎症疾病模型中使用了蛋白质组学方法来靶向蛋白质硝化。这种方法确定了40多个硝基酪氨酸免疫阳性蛋白，包括30个以前没有确定，成为修饰的炎症反应阿萨结果。这些靶点包括参与氧化应激、凋亡、ATP产生和其他代谢功能的蛋白质。我们的方法提供了一种获得硝基蛋白质组的全面观点的手段，并有望扩大对NO如何调节细胞过程的理解。
Inflammation in asthma, sepsis, transplant rejection, and many neurodegenerative diseases associates an up-regulation of NO synthesis with increased protein nitration at tyrosine. Nitration can cause protein dysfunction and is implicated in pathogenesis, but few proteins that appear nitrated in vivo have been identified. To understand how this modification impacts physiology and disease, we used a proteomic approach toward targets of protein nitration in both in vivo and cell culture inflammatory disease models. This approach identified more than 40 nitrotyrosine-immunopositive proteins, including 30 not previously identified, that became modified asa consequence of the inflammatory response. These targets include proteins involved in oxidative stress, apoptosis, ATP production, and other metabolic functions. Our approach provides a means toward obtaining a comprehensive view of the nitroproteome and promises to broaden understanding of how NO regulates cellular processes.