Characterization of cellular oxidative stress response by stoichiometric redox proteomics.
Characterization of cellular oxidative stress response by stoichiometric redox proteomics.
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通过化学计量氧化还原蛋白质组学表征细胞氧化应激反应。
DOI：
10.1152/ajpcell.00040.2020
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Qian,Wei-Jun
中科院分区：
文献类型：
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作者：
Zhang,Tong;Gaffrey,MatthewJ;Li,Xiaolu;Qian,Wei-Jun
巯基氧化还原蛋白质组是指其半胱氨酸巯基经历各种氧化还原依赖性翻译后修饰（PTM）的所有蛋白质，包括S-谷胱甘肽化（SSG）、S-亚硝基化（SNO）、S-亚磺酰化（SOH）和S-巯基化（SSH）。这些修饰可以影响蛋白质功能的各个方面，例如活性、结合、构象、定位以及与其他分子的相互作用。为了鉴定信号传导和调节中的新型氧化还原蛋白，非常需要具有稳健的氧化还原蛋白质组学方法，其可以提供氧化还原PTM的全局、位点特异性和化学计量定量。基于质谱（MS）的氧化还原蛋白质组学已成为广泛表征细胞和组织中巯基PTM的主要平台。在此，我们回顾了最近的进展，基于MS的氧化还原蛋白质组学方法的氧化还原PTM在生理或氧化应激条件下的定量分析，并强调了一些最近的应用。考虑到现有方法的相对成熟，重点将放在两种类型的修改：1）总氧化（即，所有可逆的巯基修饰），其水平代表了总的氧化还原状态，和2）S-谷胱甘肽化，可逆巯基氧化的主要形式。我们还讨论了硫醇PTM的化学计量测量的意义，以及未来的前景，以更好地了解细胞和组织中的细胞氧化还原调节网络。
The thiol redox proteome refers to all proteins whose cysteine thiols are subjected to various redox-dependent posttranslational modifications (PTMs) includingS-glutathionylation (SSG),S-nitrosylation (SNO),S-sulfenylation (SOH), andS-sulfhydration (SSH). These modifications can impact various aspects of protein function such as activity, binding, conformation, localization, and interactions with other molecules. To identify novel redox proteins in signaling and regulation, it is highly desirable to have robust redox proteomics methods that can provide global, site-specific, and stoichiometric quantification of redox PTMs. Mass spectrometry (MS)-based redox proteomics has emerged as the primary platform for broad characterization of thiol PTMs in cells and tissues. Herein, we review recent advances in MS-based redox proteomics approaches for quantitative profiling of redox PTMs at physiological or oxidative stress conditions and highlight some recent applications. Considering the relative maturity of available methods, emphasis will be on two types of modifications:1) total oxidation (i.e., all reversible thiol modifications), the level of which represents the overall redox state, and2)S-glutathionylation, a major form of reversible thiol oxidation. We also discuss the significance of stoichiometric measurements of thiol PTMs as well as future perspectives toward a better understanding of cellular redox regulatory networks in cells and tissues.