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Metabolic Brain Disease

, Volume 34, Issue 1, pp 183–189 | Cite as

Potential widespread denitrosylation of brain proteins following prolonged restraint: proposed links between stress and central nervous system disease

  • Timothy D. FoleyEmail author
  • Kari S. Koval
  • Alexandria G. Gallagher
  • Stefan H. Olsen
Original Article
  • 70 Downloads

Abstract

The biochemical pathways by which aberrant psychophysiological stress promotes neuronal damage and increases the risks for central nervous system diseases are not well understood. In light of previous findings that psychophysiological stress, modeled by animal restraint, can increase the activities and expression levels of nitric oxide synthase isoforms in multiple brain regions, we examined the effects of restraint, for up to 6 h, on levels of S-nitrosylated proteins and NOx (nitrite + nitrate), a marker for high-level nitric oxide generation, in the brains of rats. Results identify functionally-diverse protein targets of S-nitrosylation in the brain, in vivo, and demonstrate the potential for widespread loss of protein nitrosothiols following prolonged restraint despite a concomitant increase in NOx levels. Since physiological levels of protein S-nitrosylation can protect neurons by maintaining redox homeostasis, by limiting excitatory neurotransmission, and by inhibiting apoptotic and inflammatory pathways, we propose that over-activation of protein denitrosylation pathways following sustained or repeated stress may facilitate neural damage and early stages of stress-related central nervous system disease.

Keywords

Denitrosylation S-Nitrosylation Nitric oxide Psychophysiological stress 

Notes

Acknowledgements

The authors wish to thank the University of Scranton for providing the funding to support this work.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of ScrantonScrantonUSA

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