Protective effect of melatonin against the 1-methyl-4-phenylpyridinium-induced inhibition of complex I of the mitochondrial respiratory chain.
In the present study, a novel property of melatonin is shown: a protective effect of melatonin on the respiratory chain in isolated rat liver mitochondria and in striatal synaptosomes treated with 1-methyl-4-phenylpyridinium ion (MPP+). The cellular damage caused by MPP+, a compound that produces a Parkinsonian-like syndrome in humans, is the result of the mitochondrial respiration inhibition at the Complex I level and oxidative stress induction. Treatment of mitochondria with MPP+ inhibits the respiration rate. This effect was prevented by the inclusion of melatonin in the incubation mixture. This preventive effect, which is not related to the antioxidative properties of melatonin, seems to be due to the fact that melatonin prevents MPP+ interaction with Complex I. These results suggest that melatonin may protect against the effect of several Parkinsonogenic compounds that are associated with progressive impairment of mitochondrial function and increased oxidative damage.
Absi
E
E
Departamento de Bioquimica, Bromatologia y Toxicologia, Facultad de Farmacia, Universidad de Sevilla, Spain.
Ayala
A
A
Machado
A
A
Parrado
J
J
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D042967:Electron Transport Complex I; D006801:Humans; D066298:In Vitro Techniques; D008550:Melatonin / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D008550:Melatonin; D015655:1-Methyl-4-phenylpyridinium