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- Title
Potential widespread denitrosylation of brain proteins following prolonged restraint: proposed links between stress and central nervous system disease.
- Authors
Foley, Timothy D.; Koval, Kari S.; Gallagher, Alexandria G.; Olsen, Stefan H.
- 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.
- Subjects
BRAIN proteins; CENTRAL nervous system diseases; PSYCHOLOGICAL stress; NITRIC-oxide synthases; NITROSYLATION
- Publication
Metabolic Brain Disease, 2019, Vol 34, Issue 1, p183
- ISSN
0885-7490
- Publication type
Article
- DOI
10.1007/s11011-018-0340-1