Redox proteomics: from bench to bedside.

Abstract

In general protein posttranslation modifications (PTMs) involve the covalent addition of functional groups or molecules to specific amino acid residues in proteins. These modifications include phosphorylation, glycosylation, S-nitrosylation, acetylation, lipidation, among others (Angew Chem Int Ed Engl 44(45):7342-7372, 2005). Although other amino acids can undergo different kinds of oxidative posttranslational modifications (oxPTMs) (Exp Gerontol 36(9):1495-1502, 2001), in this chapter oxPTM will be considered specifically related to Cysteine oxidation, and redox proteomics here is translated as a comprehensive investigation of oxPTMs, in biological systems, using diverse technical approaches. Protein Cysteine residues are not the only amino acid that can be target for oxidative modifications in proteins (Exp Gerontol 36(9):1495-1502, 2001; Biochim Biophys Acta 1814(12):1785-1795, 2011), but certainly it is among the most reactive amino acid (Nature 468(7325):790-795, 2010). Interestingly, it is one of the least abundant amino acid, but it often occurs in the functional sites of proteins (J Mol Biol 404(5):902-916, 2010). In addition, the majority of the Cysteine oxidations are reversible, indicating potential regulatory mechanism of proteins. The global analysis of oxPTMs has been increasingly recognized as an important area of proteomics, because not only maps protein caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS), but also explores protein modulation involving ROS/RNS. Furthermore, the tools and strategies to study this type oxidation are also very abundant and developed, offering high degree of accuracy on the results. As a consequence, the redox proteomics field focuses very much on analyzing Cysteine oxidation in proteins under several experimental conditions and diseases states. Therefore, the identification and localization of oxPTMs within cellular milieu became critical to understand redox regulation of proteins in physiological and pathological conditions, and consequently an important information to develop better strategies for treatment and prevention of diseases associated with oxidative stress.There is a wide range of techniques available to investigate oxPTMs, including gel-based and non-gel-based separation approaches to be combined with sophisticated methods of detection, identification, and quantification of these modifications. The strategies and approaches to study oxPTMs and the respective applications related to physiological and pathological conditions will be discussed in more detail in this chapter.