Possible Role of Salsolinol Quinone Methide in the Decrease of RCSN-3 Cell Survival

• Published in: Biochemical and biophysical research communications Vol. 283; no. 5; pp. 1069 - 1076
• Main Authors: Martinez-Alvarado, Pedro, Dagnino-Subiabre, Alexies, Paris, Irmgard, Metodiewa, Diana, Welch, Christopher J., Olea-Azar, Claudio, Caviedes, Pablo, Caviedes, Raul, Segura-Aguilar, Juan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.05.2001
• Subjects: Animals; Biological Transport - drug effects; catalase; Catalase - genetics; Cell Line; Cell Survival - drug effects; DAT; dicoumarol; Dicumarol - pharmacology; dopamine; Dopamine - metabolism; DT-diaphorase; Electron Spin Resonance Spectroscopy; Gene Expression Regulation, Enzymologic - drug effects; glutathione peroxidase; Glutathione Peroxidase - genetics; Indolequinones; Indoles - pharmacology; Isoquinolines - pharmacology; lactoperoxidase; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; quinone methide; Quinones - pharmacology; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; salsolinol; substantia nigra; Substantia Nigra - cytology; Superoxide Dismutase - genetics; Transcription, Genetic - drug effects; salsolinol; quinone methide; substantia nigra; DAT; dicoumarol; DT-diaphorase; dopamine; lactoperoxidase; catalase; glutathione peroxidase
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2001.4907

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 μM salsolinol induced a 50% survival decrease). Incubation of RCSN-3 cells with 100 μM 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 μM salsolinol alone or in the presence of 100 μM 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.