Enhanced autoxidation of dopamine as a possible basis of manganese neurotoxicity.
Autoxidation of dopamine as measured by its aminochrome formation at 480 nm was considerably potentiated by Mn++ in comparison to other biologically-important divalent cations such as Cu++, Zn++, Ni++, Ca++ and Mg++. Effectiveness of autoxidation by metal ions tested was closely related to their redox potential. Manganese-enhanced autoxidation of dopamine was associated with increased generation of the free radicals O2-, H2O2, and HO as suggested by the inhibitory effects of superoxide dismutase, catalase and ethanol. Manganese, by enhancing the oxidation of dopamine, may augment considerably the production of neurotoxins emanating from this process and, under in vivo conditions, could be expected to contribute significantly to the neurodegenerative changes that accompany manganese dyskinesia in man.
Donaldson
J
J
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
LaBella
F S
FS
Gesser
D
D
D000818:Animals; D002384:Catalysis; D003300:Copper / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D020149:Manganese Poisoning / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
D003300:Copper; D013482:Superoxide Dismutase; D004298:Dopamine; D009638:Norepinephrine