La maladie de Parkinson en France (serveur d'exploration)

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Enantio-specific induction of apoptosis by an endogenous neurotoxin, N-methyl(R)salsolinol, in dopaminergic SH-SY5Y cells : Suppression of apoptosis by N-(2-heptyl)-N-methylpropargylamine

Identifieur interne : 001069 ( PascalFrancis/Checkpoint ); précédent : 001068; suivant : 001070

Enantio-specific induction of apoptosis by an endogenous neurotoxin, N-methyl(R)salsolinol, in dopaminergic SH-SY5Y cells : Suppression of apoptosis by N-(2-heptyl)-N-methylpropargylamine

Auteurs : W. Maruyama [Japon] ; A. A. Boulton [Canada] ; B. A. Davis [Canada] ; P. Dostert [France] ; M. Naoi [Japon]

Source :

RBID : Pascal:01-0115994

Descripteurs français

English descriptors

Abstract

Endogenous N-methyl(R)salsolinol, which caused parkinsonism in rats by injection in the striatum, was found to induce apoptosis in dopaminergic neuroblastoma SH-SY5Y cells. After 12-h incubation with 500 μM N-methyl(R)salsolinol, almost all the cells died with apoptosis and necrotic cell death was negligible. N-Methyl(R)salsolinol was much more potent to induce apoptosis than the (S)-enantiomer. The mechanism of apoptosis was studied in relation to changes in mitochondrial membrane potential, ΔΨm, using a fluorescent indicator, JC-1. Red fluorescence of J-aggregates representing hyperpolarized ΔΨm was found to decrease significantly within 60min after incubation with N-methyl(R)salsolinol, but not by the (S)-enantiomer at the same concentration. It suggests that mitochondria may recognize the stereo-chemical structure of N-methyl(R) salsolinol. Aliphatic propargylamines, (R)-N-(2-heptyl)-N-methylpropargyl-amine and (R)-N-(2-heptyl)propargylamine, were found to prevent ΔΨm loss and subsequent apoptosis induced by N-methyl(R)salsolinol. These results suggest that mitochondria play a key role in the induction of apoptosis by the neurotoxin and the prevention by aliphatic propargylamines.


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Pascal:01-0115994

Le document en format XML

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