Seizure-induced changes in mitochondrial redox status.
The aim of this study was to determine seizure-induced oxidative stress by measuring hippocampal glutathione (GSH) and glutathione disulfide (GSSG) levels in tissue and mitochondria. Kainate-induced status epilepticus (SE) in rats resulted in a time-dependent decrease of GSH/GSSG ratios in both hippocampal tissue and mitochondria. However, changes in GSH/GSSG ratios were more dramatic in the mitochondrial fractions compared to hippocampal tissue. This was accompanied by a mild increase in glutathione peroxidase activity and a decrease in glutathione reductase activity in hippocampal tissue and mitochondria, respectively. Since coenzyme A (CoASH) and its disulfide with GSH (CoASSG) are primarily compartmentalized within mitochondria, their measurement in tissue was undertaken to overcome problems associated with GSH/GSSG measurement following subcellular fractionation. Hippocampal tissue CoASH/CoASSG ratios were decreased following kainate-induced SE, the time course and magnitude of change paralleling mitochondrial GSH/GSSG levels. Cysteine, a rate-limiting precursor of glutathione was decreased following kainate administration in both hippocampal tissue and mitochondrial fractions. Together these changes in altered redox status provide further evidence for seizure-induced mitochondrial oxidative stress.
Liang
Li-Ping
LP
Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Box C238, Denver, CO 80262, USA.
Patel
Manisha
M
D000818:Animals; D003065:Coenzyme A / Q000187:drug effects / Q000378:metabolism; D003545:Cysteine / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000187:drug effects / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007608:Kainic Acid; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*; D013997:Time Factors
D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione; D003545:Cysteine; D003065:Coenzyme A; D007608:Kainic Acid; D019803:Glutathione Disulfide