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 degrees C with a second-order rate constant of 1.5 x 10(3) M(-1) x s(-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-hydroxydopamine with either bovine serum albumin or alpha-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.
Riobó
Natalia A
NA
Laboratory of Oxygen Metabolism, University Hospital, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina. nataliariobo@hotmail.com
Schöpfer
Francisco J
FJ
Boveris
Alejandro D
AD
Cadenas
Enrique
E
Poderoso
Juan J
JJ
D000818:Animals; D002417:Cattle; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D016627:Oxidopamine / Q000009:adverse effects / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D030421:Peroxynitrous Acid / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D051843:Synucleins; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; D051843:Synucleins; D051844:alpha-Synuclein; D030421:Peroxynitrous Acid; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D016627:Oxidopamine; D013482:Superoxide Dismutase