Neuroproteomic study of nitrated proteins in moderate traumatic brain injured rats treated with gamma glutamyl cysteine ethyl ester administration post injury: Insight into the role of glutathione elevation in nitrosative stress

Proteomics Clin Appl. 2016 Dec;10(12):1218-1224. doi: 10.1002/prca.201600004. Epub 2016 Nov 11.

Abstract

Purpose: The aims of this study are to establish a time point to determine the most beneficial time to administer GCEE post incident to reduce oxidative damage and second, by using redox proteomics, to determine if GCEE can readily suppress 3-NT modification in TBI animals.

Experimental design: By using a moderate traumatic brain injury model with Wistar rats, it is hypothesized that the role of 3-nitrotyrosine (3-NT) formation as an intermediate will predict the involvement of protein nitration/nitrosation and oxidative damage in the brain.

Results: In this experiment, the levels of protein carbonyls, 4-hydroxynonenal, and 3-nitrotyrosine were significantly elevated in TBI injured, saline treated rats compared with those who sustained an injury and were treated with 150 mg/kg of the glutathione mimetic, GCEE.

Conclusion and clinical relevance: Determining the existence of elevated 3-NT levels provides insight into the relationship between the protein nitration/nitrosation and the oxidative damage, which can determine the pathogenesis and progression of specific neurological diseases.

Keywords: 3-Nitrotyrosine (3-NT); Nitrosative stress; Protein nitration; Reactive nitrogen species (RNS); Traumatic brain injury (TBI).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Brain / drug effects
  • Brain / metabolism
  • Brain Injuries, Traumatic / drug therapy
  • Brain Injuries, Traumatic / metabolism*
  • Cysteine / administration & dosage
  • Cysteine / analogs & derivatives*
  • Cysteine / pharmacology
  • Cysteine / therapeutic use
  • Dipeptides
  • Male
  • Nitrates / metabolism*
  • Oxidative Stress / drug effects*
  • Protein Processing, Post-Translational / drug effects*
  • Proteomics*
  • Rats
  • Rats, Wistar

Substances

  • Antioxidants
  • Dipeptides
  • Nitrates
  • N-gamma-glutamylcysteine ethyl ester
  • ethyl cysteine
  • Cysteine