Oxygen activation during the interaction between MPTP metabolites and synthetic neuromelanin--an ESR-spin trapping, optical, and oxidase electrode study.
Oxidase electrode measurements as well as optical and electron spin resonance spectroscopic data have shown that synthetic neuromelanin oxidizes the neurotoxin metabolite 1-methyl-4-phenyl-2,3-dihydropyridinium in a dose-dependent manner forming 1-methyl-4-phenylpyridinium and hydrogen peroxide. Hydroxyl radicals are formed in this reaction which is promoted by iron chelates. In contrast, neither 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine nor 1-methyl-4-phenylpyridinium reacts with synthetic neuromelanin in a similar fashion. The mechanism of selective toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in pigmented neuronal cells is discussed in the light of these findings.
Korytowski
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W
Department of Radiology, Medical College of Wisconsin, Milwaukee 53226.
Felix
C C
CC
Kalyanaraman
B
B
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine / Q000378:metabolism; D004566:Electrodes; D004578:Electron Spin Resonance Spectroscopy; D006878:Hydroxides; D017665:Hydroxyl Radical; D008543:Melanins / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000378:metabolism
D006878:Hydroxides; D008543:Melanins; D011725:Pyridines; D011726:Pyridinium Compounds; C014121:neuromelanin; D017665:Hydroxyl Radical; C044755:1-methyl-4-phenyl-2,3-dihydropyridinium; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010088:Oxidoreductases; D010100:Oxygen; D004298:Dopamine