Antioxidant enzymes as redox-based biomarkers: a brief review

Abstract

The field of redox proteomics focuses to a large extent on analyzing cysteine oxidation in proteins under different experimental conditions and states of diseases. The identification and localization of oxidized cysteines within the cellular milieu is critical for understanding the redox regulation of proteins under physiological and pathophysiological conditions, and it will in turn provide important information that are potentially useful for the development of novel strategies in the treatment and prevention of diseases associated with oxidative stress. Antioxidant enzymes that catalyze oxidation/reduction processes are able to serve as redox biomarkers in various human diseases, and they are key regulators controlling the redox state of functional proteins. Redox regulators with antioxidant properties related to active mediators, cellular organelles, and the surrounding environments are all connected within a network and are involved in diseases related to redox imbalance including cancer, ischemia/reperfusion injury, neurodegenerative diseases, as well as normal aging. In this review, we will briefly look at the selected aspects of oxidative thiol modification in antioxidant enzymes and thiol oxidation in proteins affected by redox control of antioxidant enzymes and their relation to disease.

Fig. 1.. Oxidative post-translational modification of cysteine residues in proteins. Cysteine is commonly located on the surface and at the active site of proteins, either alone (monothiols) or in close proximity to another cysteine residue (vicinal dithiols). Vicinal dithiols tend to form disulfides upon oxidation, whereas monothiols undergo reversible oxidation to sulfenic acid. Under strongly oxidizing conditions, sulfenic acid is further oxidized to sulfinic and sulfonic acids. Other modifications that also occur include acetylation, glutathionylation, nitrosylation, and carbonylation of protein cysteines. These changes can result in alterations in protein-protein interactions, enzyme activity, DNA and/or RNA binding, and membrane interactions. HNE, 4hydroxynonenal; ROS, reactive oxygen species.