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.

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[microM 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, deltapsi(m), using a fluorescent indicator, JC-1. Red fluorescence of J-aggregates representing hyperpolarized deltapsi(m) was found to decrease significantly within 60 min 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-methylpropargylamine and (R)-N-(2-heptyl)propargylamine, were found to prevent deltapsim 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.

• Authors: W Maruyama, A A Boulton, B A Davis, P Dostert, M Naoi
• Journal: Journal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 108 Issue 1 Pg. 11-24 ( 2001) ISSN: 0300-9564 [Print] Austria
• PMID: 11261742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkynes
• Fluorescent Dyes
• Monoamine Oxidase Inhibitors
• N-2-heptyl-N-methylpropargylamine
• Neuroprotective Agents
• Neurotoxins
• Salsoline Alkaloids
• Tetrahydroisoquinolines
• salsoline
• Dopamine

Topics

• Alkynes (pharmacology)
• Apoptosis (drug effects, physiology)
• Dopamine (metabolism)
• Drug Interactions (physiology)
• Fluorescent Dyes
• Humans
• Membrane Potentials (drug effects, physiology)
• Mitochondria (drug effects, metabolism, pathology)
• Monoamine Oxidase Inhibitors (pharmacology)
• Neuroblastoma
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (pharmacology)
• Neurotoxins (pharmacology)
• Parkinsonian Disorders (chemically induced, physiopathology, prevention & control)
• Salsoline Alkaloids (pharmacology)
• Signal Transduction (drug effects, physiology)
• Stereoisomerism
• Substantia Nigra (drug effects, metabolism, physiopathology)
• Tetrahydroisoquinolines
• Tumor Cells, Cultured (cytology, drug effects, metabolism)