Protective effect of N-(2-propynyl)-2-(5-benzyloxyindolyl) methylamine (PF 9601N), a novel MAO-B inhibitor, on dopamine-lesioned PC12 cultured cells.
Oxidative stress may play a role in the pathogenesis of Parkinson's disease. We have standardised a new model of dopaminergic-cell toxicity that uses dopamine, which is able to generate free radicals, as a toxin. The effect of this catecholamine on cell viability (MTT staining) was dose-dependent, reaching 65% of cell loss at a dopamine concentration of 300 microM. In this model, the protective effect of a novel MAO-B inhibitor, N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine (PF 9601N), was studied and compared with the effect of L-deprenyl assayed under the same experimental conditions. Whereas PF 9601N (50 microM and 100 microM) showed a significant protective effect, this was not the case with L-deprenyl. This different behaviour could be explained in terms of difference in antioxidant capacity. The toxicity induced in PC12 cells by 300 microM dopamine was partially reversed by incubating it in the presence of GBR-12909, a dopamine-transporter blocker. The results indicated that, besides the intracellular toxicity effect of dopamine, another non-specific extracellular mechanism could be involved.
Perez
V
V
Depart. Bioquímica i Biologia Molecular, Fac. Medicina, Universitat Autónoma de Barcelona, Bellaterra 08193, Spain.
Romera
M
M
Lizcano
J M
JM
Marco
J L
JL
Unzeta
M
M
D000818:Animals; D002470:Cell Survival; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000633:toxicity*; D007211:Indoles / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats
D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; C470996:N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine; D008995:Monoamine Oxidase; D004298:Dopamine