γ-glutamyl cysteine synthetase is up-regulated during recovery of brain mitochondrial complex I following neurotoxic insult in mice

Rajappa S. Kenchappa, Vijayalakshmi Ravindranath

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

β-N-Oxalyl amino-L-alanine (L-BOAA), a naturally occurring excitatory amino acid inhibits mitochondrial complex I activity in motor cortex and lumbar spinal cord of mice through oxidation of critical thiol groups. Glutaredoxin, a protein disulfide oxido-reductase mediates recovery of complex I by regenerating protein thiols utilizing reducing equivalents of glutathione. We have examined the status of γ-glutamyl cysteine synthetase (γ-GCS), the rate limiting enzyme in glutathione synthesis during recovery of complex I function following L-BOAA toxicity. Sustained and maximal up-regulation of γ-GCS was seen in motor cortex which was associated with regeneration of complex I activity. In lumbosacral cord, however, the up-regulation was transient and complex I function did not recover. These studies demonstrate the important role of γ-GCS in mediating the recovery of mitochondrial function following excitotoxic insult and its differential regulation in central nervous system regions.

Original languageEnglish (US)
Pages (from-to)51-55
Number of pages5
JournalNeuroscience Letters
Volume350
Issue number1
DOIs
StatePublished - Oct 16 2003

Keywords

  • Brain
  • Complex I
  • Excitatory amino acid
  • Glutathione
  • Mitochondria
  • Oxidative stress
  • Thiol oxidation
  • γ-Glutamyl cysteine synthetase

ASJC Scopus subject areas

  • Neuroscience(all)

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