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Manganese neurotoxicity: effects of varying oxygen tension and EDTA on dopamine auto-oxidation
Abstract:
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.
Insights
Excess manganese (Mn) accelerates dopamine oxidation, contributing to parkinsonism. This study shows Mn significantly increases dopamine auto-oxidation rates, especially under oxygen, suggesting a role for reactive oxygen species in Mn-induced neurotoxicity.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Manganese (Mn) is essential but toxic in excess, causing parkinsonism.
- Mn is a potent stimulator of dopamine (DA) auto-oxidation compared to other metals.
Purpose of the Study:
- To investigate the effect of manganese on dopamine auto-oxidation rates.
- To explore the influence of oxygen levels and chelating agents on this process.
Main Methods:
- Incubation of manganese and dopamine at 37°C.
- Measurement of optical density at 480 nm to quantify aminochrome formation.
- Varying partial pressures of oxygen (pO2) and using EDTA as a chelating agent.
Main Results:
- Mn significantly increased DA auto-oxidation rates, particularly under elevated oxygen.
- Air plus Mn showed a 5-fold greater oxidation rate than air or Mn alone.
- EDTA reduced Mn-stimulated DA auto-oxidation by 80%.
Conclusions:
- Results support the role of activated oxygen metabolites in dopamine depletion during chronic Mn intoxication.
- Understanding Mn's effect on dopamine oxidation is crucial for neurodegenerative disease research.