Wall Stephanie B, Smith M Ryan, Ricart Karina, Zhou Fen, Vayalil Praveen K, Oh Joo-Yeun, Landar Aimee
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Biochim Biophys Acta. 2014 Feb;1840(2):913-22. doi: 10.1016/j.bbagen.2013.09.003. Epub 2013 Sep 8.
Redox signaling is an important emerging mechanism of cellular function. Dysfunctional redox signaling is increasingly implicated in numerous pathologies, including atherosclerosis, diabetes, and cancer. The molecular messengers in this type of signaling are reactive species which can mediate the post-translational modification of specific groups of proteins, thereby effecting functional changes in the modified proteins. Electrophilic compounds comprise one class of reactive species which can participate in redox signaling. Electrophiles modulate cell function via formation of covalent adducts with proteins, particularly cysteine residues.
This review will discuss the commonly used methods of detection for electrophile-sensitive proteins, and will highlight the importance of identifying these proteins for studying redox signaling and developing novel therapeutics.
There are several methods which can be used to detect electrophile-sensitive proteins. These include the use of tagged model electrophiles, as well as derivatization of endogenous electrophile-protein adducts.
In order to understand the mechanisms by which electrophiles mediate redox signaling, it is necessary to identify electrophile-sensitive proteins and quantitatively assess adduct formation. Strengths and limitations of these methods will be discussed. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.
氧化还原信号传导是细胞功能中一种重要的新兴机制。功能失调的氧化还原信号传导越来越多地与多种病理状况相关,包括动脉粥样硬化、糖尿病和癌症。这类信号传导中的分子信使是活性物质,它们可以介导特定蛋白质组的翻译后修饰,从而影响被修饰蛋白质的功能变化。亲电化合物是一类能够参与氧化还原信号传导的活性物质。亲电试剂通过与蛋白质,特别是半胱氨酸残基形成共价加合物来调节细胞功能。
本综述将讨论检测亲电试剂敏感蛋白的常用方法,并强调识别这些蛋白对于研究氧化还原信号传导和开发新型疗法的重要性。
有几种方法可用于检测亲电试剂敏感蛋白。这些方法包括使用标记的模型亲电试剂,以及对内源性亲电试剂 - 蛋白质加合物进行衍生化。
为了理解亲电试剂介导氧化还原信号传导的机制,有必要识别亲电试剂敏感蛋白并定量评估加合物的形成。将讨论这些方法的优点和局限性。本文是名为“研究活性氧的当前方法 - 利弊与膜蛋白生物物理学”的特刊的一部分。客座编辑:克里斯汀·温特伯恩。