MPTP, MPP+ and mitochondrial function
| Autor: | Stephen K. Youngster, M V Kindt, Richard E. Heikkila, William J. Nicklas |
|---|---|
| Rok vydání: | 1987 |
| Předmět: |
1-Methyl-4-phenylpyridinium
Pyridines animal diseases Metabolite Pyridinium Compounds In Vitro Techniques General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Mice Structure-Activity Relationship Oxygen Consumption Selegiline Neurotoxin Animals cardiovascular diseases General Pharmacology Toxicology and Pharmaceutics MPTP Brain General Medicine Corpus Striatum nervous system diseases Mitochondria Rats Kinetics nervous system chemistry Biochemistry Liver Anaerobic glycolysis 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Toxicity cardiovascular system NAD+ kinase Monoamine oxidase B Glycolysis |
| Zdroj: | Life sciences. 40(8) |
| ISSN: | 0024-3205 |
| Popis: | 1-Methyl-4-phenylpyridinium (MPP+), the putative toxic metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), inhibited NAD(H)-linked mitochondrial oxidation at the level of Complex I of the electron transport system. MPTP and MPP+ inhibited aerobic glycolysis in mouse striatal slices, as measured by increased lactate production; MPTP-induced effects were prevented by inhibition of monoamine oxidase B activity. Several neurotoxic analogs of MPTP also form pyridinium metabolites via MAO; these MPP+ analogs were all inhibitors of NAD(H)-linked oxidation by isolated mitochondria. 2'-Methyl-MPTP, a more potent neurotoxin in mice than MPTP, was also more potent than MPTP in inducing lactate accumulation in mouse brain striatal slices. Overall, the studies support the hypothesis that compromise of mitochondrial oxidative capacity is an important factor in the mechanisms underlying the toxicity of MPTP and similar compounds. |
| Databáze: | OpenAIRE |
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