One-Electron Reduction of 6-Hydroxydopamine Quinone is Essential in 6-Hydroxydopamine Neurotoxicity
Author/s
Villa, Mónica; Muñoz, Patricia; Ahumada Castro, Ulises; Paris, Irmgard; Jiménez, Ana; [et al.]Date
2013Discipline/s
Ciencias AmbientalesSubject/s
6-HydroxydopamineQuinone metabolism
Dopamine
Oxidation
Quinone
Parkinson’s disease
Glutathione
Abstract
6-Hydroxydamine has widely been used as neurotoxin in preclinical studies related on the neurodegenerative process of dopaminergic neurons in Parkinson’s disease based on its ability to be neurotoxic as a consequence of free radical formation during its auto-oxidation to topaminequinone. We report that 50-µM 6-hydroxydopamine is not neurotoxic in RCSN-3 cells derived from substantia nigra incubated during 24 h contrasting with a significant sixfold increase in cell death (16 ± 2 %; P < 0.001) was observed in RCSN-3NQ7 cells expressing a siRNA against DT-diaphorase that silence the enzyme expression. To observe a significant cell death in RCSN-3 cells induced by 6-hydroxydopamine (24 ± 1 %; P < 0.01), we have to increase the concentration to 250 μm while a 45 ± 2 % cell death (P < 0.001) was observed at this concentration in RCSN-3NQ7 cells. The cell death induced by 6-hydroxydopamine in RCSN-3NQ7 cells was accompanied with a (i) significant increase in oxygen consumption (P < 0.01), (i...