Functional roles of protein nitration in acute and chronic liver diseases.

Functional roles of protein nitration in acute and chronic liver diseases.
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蛋白质硝化在急性和慢性肝病中的功能作用。

DOI:
10.1155/2014/149627
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发表时间:
2014
影响因子:
--
通讯作者:
Song BJ
Song BJ
中科院分区:
生物学2区
文献类型:
--
作者:
Abdelmegeed MA;Song BJ

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当一氧化氮与超氧化物结合时,产生过氧亚硝酸盐,这是已知的包括各种肝脏疾病在内的许多疾病的重要介质。过氧亚硝酸盐可以修饰许多蛋白质的酪氨酸残基,导致蛋白质硝化,从而改变每个目标蛋白质的结构和功能。各种蛋白质组学和免疫学方法,包括质谱结合高压液相色谱和2D PAGE,已被用于鉴定和表征病理组织样品中的硝化蛋白,以确定其作用。然而,这些方法包含一些技术问题,如低效率和检测有限数量的硝化蛋白质和劳动强度。因此,有效识别硝化蛋白并表征其功能作用的系统方法可能为了解肝病病理生理机制和随后的新治疗方法的开发提供新的见解。本文就肝脏疾病的发病机制作一综述。此外,我们特别描述了一种系统的方法来有效地识别硝化蛋白,以研究它们在促进急性和慢性肝脏疾病(包括酒精性和非酒精性脂肪性肝病)中的因果作用或功能后果。我们最后通过分析硝化蛋白在评估潜在有益药物预防或治疗肝脏和其他组织中各种疾病的功效方面的应用,讨论了转化研究的应用。
Nitric oxide, when combined with superoxide, produces peroxynitrite, which is known to be an important mediator for a number of diseases including various liver diseases. Peroxynitrite can modify tyrosine residue(s) of many proteins resulting in protein nitration, which may alter structure and function of each target protein. Various proteomics and immunological methods including mass spectrometry combined with both high pressure liquid chromatography and 2D PAGE have been employed to identify and characterize nitrated proteins from pathological tissue samples to determine their roles. However, these methods contain a few technical problems such as low efficiencies with the detection of a limited number of nitrated proteins and labor intensiveness. Therefore, a systematic approach to efficiently identify nitrated proteins and characterize their functional roles is likely to shed new insights into understanding of the mechanisms of hepatic disease pathophysiology and subsequent development of new therapeutics. The aims of this review are to briefly describe the mechanisms of hepatic diseases. In addition, we specifically describe a systematic approach to efficiently identify nitrated proteins to study their causal roles or functional consequences in promoting acute and chronic liver diseases including alcoholic and nonalcoholic fatty liver diseases. We finally discuss translational research applications by analyzing nitrated proteins in evaluating the efficacies of potentially beneficial agents to prevent or treat various diseases in the liver and other tissues.
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