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Possible role of salsolinol quinone methide in the decrease of RCSN-3 cell survival.

P Martinez-Alvarado·A Dagnino-Subiabre·I Paris·D Metodiewa·C J Welch·C Olea-Azar·P Caviedes·R Caviedes·J Segura-Aguilar
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Abstract

The endogenous dopamine-derived neurotoxin salsolinol was found to decrease survival in the dopaminergic neuronal cell line RCSN-3, derived from adult rat substantia nigra in a concentration-dependent manner (208 microM salsolinol induced a 50% survival decrease). Incubation of RCSN-3 cells with 100 micro;M dicoumarol and salsolinol significantly decreased cell survival by 2.5-fold (P < 0.001), contrasting with a negligible effect on RCHT cells, which exhibited nearly a 5-fold lower nomifensine-insensitive dopamine uptake. The levels of catalase and glutathione peroxidase mRNA were decreased when RCSN-3 cells were treated with 100 microM salsolinol alone or in the presence of 100 microM dicoumarol. In vitro oxidation of salsolinol to o-quinone catalyzed by lactoperoxidase gave the quinone methide and 1,2-dihydro-1-methyl-6,7-isoquinoline diol as final products of salsolinol oxidation as determined by NMR analysis. Evidence of the formation of salsolinol o-semiquinone radical has been provided by ESR studies during one-electron oxidation of salsolinol catalyzed by lactoperoxidase.

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AnimalsBiological TransportCatalaseCell LineCell SurvivalDicumarolDopamineElectron Spin Resonance SpectroscopyGene Expression Regulation, EnzymologicGlutathione PeroxidaseIndolequinonesIndolesIsoquinolinesNeuronsQuinonesRNA, MessengerRatsReverse Transcriptase Polymerase Chain ReactionSubstantia NigraSuperoxide DismutaseTranscription, GeneticJournal ArticleResearch Support, Non-U.S. Gov't

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P Martinez-Alvarado, A Dagnino-Subiabre, I Paris, D Metodiewa, C J Welch, C Olea-Azar, P Caviedes, R Caviedes, J Segura-Aguilar. 2001-05-25. Possible role of salsolinol quinone methide in the decrease of RCSN-3 cell survival.. https://doi.org/10.1006/bbrc.2001.4907

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