Oxidative mechanisms involved in kainate-induced cytotoxicity in cortical neurons.
In our previous experiments, evidence of free radical formation has been demonstrated in gerbil brain after kainic acid (KA) administration. In the present study, the mechanisms involved in KA-induced free radical formation and subsequent cell degeneration were investigated using high density cortical neuron cultures. A free radical trapping agent, alpha-phenyl-N-tert- butyl-nitrone (PBN), as well as the combined action of superoxide dismutase and catalase attenuated KA neurotoxic effect. Calpain-induced xanthine oxidase (XO) activation may play an important role in KA excitotoxicity since calpain inhibitor I as well as allopurinol, a selective XO inhibitor, significantly protected the cortical neurons from KA-induced cell death. However, XO activation may not be the only source producing free radicals, other free radical generating systems such as nitric oxide synthase may also play a role in KA insult.
Cheng
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Department of Pharmacology, University of Missouri-Columbia School of Medicine 65212.
Sun
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D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002154:Calpain / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003497:Cyclic N-Oxides; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D016166:Free Radical Scavengers; D005609:Free Radicals; D006023:Glycoproteins / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000494:pharmacology; D010084:Oxidation-Reduction; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D006023:Glycoproteins; D009589:Nitrogen Oxides; C039304:calpain inhibitors; C029217:phenyl-N-tert-butylnitrone; D000493:Allopurinol; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D002154:Calpain; D007608:Kainic Acid