Manganese neurotoxicity: effects of varying oxygen tension and EDTA on dopamine auto-oxidation.
Manganese (Mn) is an essential trace element which, in excess, induces a chronic parkinsonian disease in animals and humans. Previous work indicated that Mn was more potent than other transition metal ions at stimulating dopamine (DA) auto-oxidation. We incubated Mn and DA at 37 degrees C and observed optical density changes at 480 nm, which is proportional to aminochrome formation. pO2 was held at O(N2), 160(O2), or 720 mm Hg(95%O2). Air without Mn produced approximately the same oxidation rate as Mn under N2; air plus Mn (33 uM) yielded a rate 5-fold greater than either air or Mn alone. Under elevated pO2, Mn (10 uM) produced approximately twice the rate seen with air. Addition of the chelating agent (EDTA, 1 mM) produced an 80% decrease in Mn-stimulated DA auto-oxidation. Results are consistent with a role for activated oxygen metabolites in DA depletion seen in chronic Mn intoxication.
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology*; D006801:Humans; D020149:Manganese Poisoning; D009420:Nervous System / Q000187:drug effects*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*
D004492:Edetic Acid; D010100:Oxygen; D004298:Dopamine