Neurochemical Research

, Volume 39, Issue 11, pp 2030–2039 | Cite as

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

  • Timothy D. FoleyEmail author
  • Kristen M. Cantarella
  • Paul F. Gillespie
  • Edward S. Stredny
Original Paper


Reversible oxidations of protein thiols have emerged as alternatives to free radical-mediated oxidative damage with which to consider the impacts of oxidative stress on cellular activities but the scope and pathways of such oxidations in tissues, including the brain, have yet to be fully defined. We report here a characterization of reversible oxidations of glutathione and protein thiols in extracts from rat brains, from two sources, which had been (1) frozen quickly after euthanasia to preserve in vivo redox states and (2) subjected to alkylation upon tissue disruption to trap reduced thiols. Brains were defined, relatively, as Reduced and Moderately Oxidized based on measured ratios of reduced (GSH) to oxidized (GSSG) glutathione. Levels of protein disulfides formed by the cross-linking of closely-spaced (vicinal) protein thiols, but not protein S-glutathionylation, were higher in extracts from the Moderately Oxidized brains compared to the Reduced brains. Moreover, the oxidized vicinal thiol proteome contains proteins that impact cellular energetics, signaling, neurotransmission, and cytoskeletal dynamics among others. These findings argue that kinetically-competent pathways for reversible, two-electron oxidations, of protein vicinal thiols can be activated in healthy brains in response to physiological oxidative stresses. We propose that such oxidations may link oxidative stress to adaptive, but also potentially deleterious, changes in neural cell activities in otherwise healthy brains.


Glutathione Oxidative stress Protein disulfides Protein S-glutathionylation Vicinal thiols 


Conflict of interest

The authors declare that they have no conflict of interest.

Animal and human rights

Experiments involving animals were approved by the University of Scranton Institutional Animal Care and Use Committee in accordance with ethical standards for the use of animals in scientific research.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Timothy D. Foley
    • 1
    Email author
  • Kristen M. Cantarella
    • 1
  • Paul F. Gillespie
    • 1
  • Edward S. Stredny
    • 1
  1. 1.Biochemistry Program, Department of ChemistryUniversity of ScrantonScrantonUSA

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