TY - JOUR
T1 - γ-glutamyl cysteine synthetase is up-regulated during recovery of brain mitochondrial complex I following neurotoxic insult in mice
AU - Kenchappa, Rajappa S.
AU - Ravindranath, Vijayalakshmi
N1 - Funding Information:
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.
PY - 2003/10/16
Y1 - 2003/10/16
N2 - 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.
AB - 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.
KW - Brain
KW - Complex I
KW - Excitatory amino acid
KW - Glutathione
KW - Mitochondria
KW - Oxidative stress
KW - Thiol oxidation
KW - γ-Glutamyl cysteine synthetase
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U2 - 10.1016/S0304-3940(03)00779-1
DO - 10.1016/S0304-3940(03)00779-1
M3 - Article
C2 - 12962915
AN - SCOPUS:0142106908
SN - 0304-3940
VL - 350
SP - 51
EP - 55
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1
ER -