Elsevier

Neuroscience Letters

Volume 350, Issue 1, 16 October 2003, Pages 51-55
Neuroscience Letters

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

https://doi.org/10.1016/S0304-3940(03)00779-1Get rights and content

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.

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Acknowledgements

We thank Dr T. Kavanagh, University of Washington for the gift of the cDNA to the heavy subunit of γ-GCS. We also thank Ms L. Diwakar and S.N. Hegde for their help with some experiments. This work was funded by the US India fund for cultural, educational and scientific co-operation.

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