Gamma-glutamyl cysteine synthetase is up-regulated during recovery of brain mitochondrial complex I following neurotoxic insult in mice.
Beta-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 gamma-glutamyl cysteine synthetase (gamma-GCS), the rate limiting enzyme in glutathione synthesis during recovery of complex I function following L-BOAA toxicity. Sustained and maximal up-regulation of gamma-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 gamma-GCS in mediating the recovery of mitochondrial function following excitotoxic insult and its differential regulation in central nervous system regions.
Kenchappa
Rajappa S
RS
National Brain Research Centre, Nainwal Mode, Manesar, 122050 Haryana, India.
Ravindranath
Vijayalakshmi
V
D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D018846:Excitatory Amino Acids / Q000633:toxicity*; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism*; D005981:Glutathione Synthase / Q000032:analysis / Q000235:genetics*; D008161:Lumbosacral Region / Q000502:physiology; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D009044:Motor Cortex / Q000187:drug effects / Q000201:enzymology; D012313:RNA / Q000032:analysis; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000633:toxicity*
D018846:Excitatory Amino Acids; D015091:beta-Alanine; D012313:RNA; D005721:Glutamate-Cysteine Ligase; D005981:Glutathione Synthase