A redox reaction between MPP+ and MPDP+ to produce superoxide radicals does not impair mitochondrial function.
Rat brain mitochondria were incubated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its two metabolites (1-methyl-4-phenyl-2,3-dihydropyridium (MPDP+) and 1-methyl-4-phenylpyridinium (MPP+), and O2 uptake was assessed. MPP+ (500 and 1000 microM) inhibited state 3 and state 4 respiration with a reduction in the respiratory control ratio (RCR). In the presence of MPTP or MPDP+ (100-1000 microM) no inhibition of mitochondrial function occurred. Incubation with MPP+ (100-1000 microM) in combination with equimolar concentrations of MPDP+ or MPTP (100-1000 microM) did not increase the inhibition of mitochondrial function produced by MPP+ alone. Inhibition of mitochondrial function produced by MPP+ (500 microM) was not reduced by incorporation of superoxide dismutase (SOD) (50-1000 units/mL). However, the RCR in the presence of 500 microM MPP+ and 1000 units/mL SOD was not different from control values. SOD did not prevent the inhibition of state 3 and state 4 respiration produced by the combination of MPP+ and MPDP+. The results suggest that a redox reaction between MPP+ and MPDP+ to generate superoxide radicals does not contribute to the impairment of mitochondrial function produced by MPTP administration.
Walker
M J
MJ
Parkinson's Disease Society Experimental Research Laboratories, Biomedical Sciences Division, King's College, London, U.K.
Jenner
P
P
Marsden
C D
CD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism; D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005609:Free Radicals; D020267:MPTP Poisoning; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D011726:Pyridinium Compounds / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
D005609:Free Radicals; D011726:Pyridinium Compounds; D013481:Superoxides; C044755:1-methyl-4-phenyl-2,3-dihydropyridinium; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D013482:Superoxide Dismutase; D015655:1-Methyl-4-phenylpyridinium