Protein Vicinal Thiol Oxidations in the Healthy Brain: Not So Radical Links between Physiological Oxidative Stress and Neural Cell Activity

The physiological and pathological roles of reactive oxygen species (ROS) in the brain are still unclear. In this study, the redox states of extracts from two populations of rat brains, that were treated to preserve in vivo redox states and prevent postmortem oxidation, were determined. Based on the GSH/GSSG ratios, these populations were biochemically defined as Reduced and Moderately Oxidized. A significant increase in the oxidation of vicinal (closely spaced) protein thiols to disulfides, but not S-glutathionylation of thiol-containing proteins, was observed in the Moderately Oxidized brains compared to the Reduced brains. The oxidized vicinal thiol proteome of these disulfide-containing proteins contains a great deal of proteins that are directly involved in ATP production and consumption. These results argue that kinetically-competent pathways for protein thiol oxidations do exist in vivo and that these reversible, two-electron oxidations occur in response to moderate physiological oxidative stress to adapt to changes in cellular metabolism