Chasing Cysteine Oxidative Modifications
Proteomic Tools for Characterizing Cysteine Redox Status
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Redox proteomics involves the large-scale analysis of oxidative protein posttranslational modifications. In particular, cysteine residues have become the subject of intensifying research because of their redox-reactive thiol side chain. Certain reactive cysteine residues can function as redox switches, which sense changes in the local redox environment by flipping between the reduced and oxidized state. Depending on the reactive oxygen or nitrogen species, cysteine residues can receive one of several oxidative modifications, each with the potential to confer a functional effect. Modification of these redox switches has been found to play an important role in oxidative signaling in the cardiovascular system and elsewhere. Because of the labile and dynamic nature of these modifications, several targeted approaches have been developed to enrich, identify, and characterize the status of these critical residues. Here, we review the various proteomic strategies and limitations for the large-scale analysis of the different oxidative cysteine modifications.
Reactive oxygen and nitrogen species (RO/NS) have been found to play a dual role in the cardiovascular system, acting both as second messengers in physiological redox signaling and as agents of oxidative damage, leading to pathological conditions.1,2 This dual role is determined largely by the balance of oxidant production and the capacity of the cell’s antioxidant defense. RO/NS in cardiomyocytes can be produced by several sources, including, in the mitochondria, nicotinamide adenine dinucleotide phosphate oxidases and NO synthases.3–5 The levels of these species are held in check by antioxidant scavengers such as catalase, glutathione (GSH) peroxidase, superoxide dismutase, peroxiredoxin, and free GSH, which patrol the cell neutralizing them.6 Changes in redox balance occur when the levels of RO/NS production exceed the local antioxidant capacity. Small changes in the concentration of some species (eg, superoxide, hydrogen peroxide, or NO) are more likely to participate in redox-signaling …