Roles of Glutathione (GSH) in Dopamine (DA) Oxidation Studied by Improved Tandem HPLC Plus ESI-MS

In this study, new procedure with improved tandem HPLC plus ESI-MS was utilized to decipher the protective role of glutathione (GSH) against dopamine (DA) oxidation. We demonstrated that auto-oxidation of DA could produce aminochrome (AM, a cyclized DA quinone), which could be effectively abrogated by reductants, especially by GSH. Furthermore GSH was demonstrated to be able to conjugate with AM to form various conjugates via condensation reactions without enzymatic catalysis. The GSH-AM conjugates tend to aggregate, possibly mediated by conjugated AM structures, but could be inhibited by GSH. We hypothesized that proteins conjugated by AM might facilitate Lewy body formation of Parkinson's disease (PD) in dopaminergic neurons via similar polymerization. We proposed that GSH could protect dopaminergic neurons against DA-induced toxicity via various mechanisms. The imbalance between DA oxidation and GSH protective capacity could be a key factor contributing to PD. Strategies to use GSH analogues, GSH inducers or to control DA oxidation might work to control PD onset and development.