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质谱分析与氧化还原蛋白质组学:在疾病中的应用

Mass spectrometry and redox proteomics: applications in disease.

作者信息

Butterfield D Allan, Gu Liqing, Di Domenico Fabio, Robinson Renã A S

机构信息

Department of Chemistry, Center of Membrane Sciences, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, 40506.

出版信息

Mass Spectrom Rev. 2014 Jul-Aug;33(4):277-301. doi: 10.1002/mas.21374. Epub 2013 Sep 30.

Abstract

Proteomics techniques are continuously being developed to further understanding of biology and disease. Many of the pathways that are relevant to disease mechanisms rely on the identification of post-translational modifications (PTMs) such as phosphorylation, acetylation, and glycosylation. Much attention has also been focused on oxidative PTMs which include protein carbonyls, protein nitration, and the incorporation of fatty acids and advanced glycation products to amino acid side chains, amongst others. The introduction of these PTMs in the cell can occur due to the attack of reactive oxygen and nitrogen species (ROS and RNS, respectively) on proteins. ROS and RNS can be present as a result of normal metabolic processes as well as external factors such as UV radiation, disease, and environmental toxins. The imbalance of ROS and RNS with antioxidant cellular defenses leads to a state of oxidative stress, which has been implicated in many diseases. Redox proteomics techniques have been used to characterize oxidative PTMs that result as a part of normal cell signaling processes as well as oxidative stress conditions. This review highlights many of the redox proteomics techniques which are currently available for several oxidative PTMs and brings to the reader's attention the application of redox proteomics for understanding disease pathogenesis in neurodegenerative disorders and others such as cancer, kidney, and heart diseases.

摘要

蛋白质组学技术不断发展,以进一步加深对生物学和疾病的理解。许多与疾病机制相关的途径依赖于对翻译后修饰(PTM)的鉴定,如磷酸化、乙酰化和糖基化。氧化型PTM也备受关注,其中包括蛋白质羰基化、蛋白质硝化以及脂肪酸和晚期糖基化终产物掺入氨基酸侧链等。细胞中这些PTM的引入可能是由于活性氧和活性氮(分别为ROS和RNS)对蛋白质的攻击。ROS和RNS可能因正常代谢过程以及紫外线辐射、疾病和环境毒素等外部因素而存在。ROS和RNS与细胞抗氧化防御的失衡会导致氧化应激状态,这与许多疾病有关。氧化还原蛋白质组学技术已用于表征作为正常细胞信号传导过程以及氧化应激条件一部分而产生的氧化型PTM。本综述重点介绍了目前可用于多种氧化型PTM的许多氧化还原蛋白质组学技术,并提请读者注意氧化还原蛋白质组学在理解神经退行性疾病以及癌症、肾脏和心脏病等其他疾病发病机制方面的应用。

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