The effects of 6-hydroxydopamine and oxidative stress on the level of brain metallothionein.
Oxidative stress, resulting either from excess generation or reduced scavenging of free radicals, has been proposed to play a role in damaging striatal neurons in Parkinson's disease. Since metallothionein is able to regulate the intracellular redox potential, we have undertaken a group of experiments to see whether or not 6-hydroxydopamine, which generates free radicals and is toxic to dopaminergic neurons, could alter the level of zinc and metallothionein. 6-Hydroxydopamine (8 micrograms in 4 microliters 0.02% ascorbic acid) reduced the level of zinc and metallothionein in the striatum but not other brain regions tested. Dopamine plus selegiline increased the synthesis of metallothionein in Chang cells as judged by enhanced incorporation of [35S]cysteine into metallothionein. The effect of dopamine was selective, in that dopamine could not stimulate the synthesis of metallothionein in neuroblastoma IMR-32 cells, which are devoid of dopaminergic receptors. The effect of dopamine in stimulating the synthesis of metallothionein was similar to that of zinc, known to generate the synthesis of metallothionein, and to that of H2O2 and FeS04, known to generate free radicals. The results of these experiments provide additional evidence that zinc or zinc metallothionein are altered in conditions where oxidative stress has taken place.
Shiraga
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Section of Neurology, University of Nebraska College of Medicine, Omaha 68198.
Pfeiffer
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Ebadi
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D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D004338:Drug Combinations; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology; D013431:Sulfates / Q000494:pharmacology; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D017967:Zinc Compounds / Q000494:pharmacology; D019287:Zinc Sulfate
D004338:Drug Combinations; D017382:Reactive Oxygen Species; D013431:Sulfates; D017967:Zinc Compounds; D012642:Selegiline; D019287:Zinc Sulfate; D016627:Oxidopamine; D008668:Metallothionein; D004298:Dopamine