The reaction of nitric oxide with 6-hydroxydopamine: implications for Parkinson’s disease

Oxidation of catecholamines is suggested to contribute to oxidative stress in Parkinson’s disease. Nitric oxide (√NO) is able to oxidize cyclic compounds like ubiquinol; moreover, recent lines of evidence proposed a direct role of √NO and its by-product peroxynitrite in the pathophysiology of Parkinson’s disease. The aim of this study was to analyze the potential reaction between 6-hydroxydopamine, a classic inducer of Parkinson’s disease, and √NO. The results showed that √NO reacts with the deprotonated form of 6-hydroxydopamine at pH 7 and 37°C with a second-order rate constant of 1.5 × 103 M−1s−1 as calculated by the rate of √NO decay measured with an amperometric sensor. Accordingly, the rates of formation of 6-hydroxy-dopamine quinone were dependent on √NO concentration. The coincubation of √NO and 6-hydro-xydopamine with either bovine serum albumin or α-synuclein led to tyrosine nitration of the protein, in a concentration dependent-manner and sensitive to superoxide dismutase. These findings suggest the formation of peroxynitrite during the redox reactions following the interaction of 6-hydroxydopamine with √NO. The implications of this reaction for in vivo models are discussed in terms of the generation of reactive nitrogen and oxygen species within a propagation process that may play a significant role in neurodegenerative diseases.