INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Nitric oxide reacts with catecholamines yielding peroxynitrite
Autor/es:
NA.RIOBÓ, FJ SCHÖPFER, EM GATTO AND JJ PODEROSO
Lugar:
Estocolmo, Suecia
Reunión:
Congreso; 6th International Meeting, Biology of Nitric Oxide; 1999
Institución organizadora:
NO Society
Resumen:
Most evidences suggest that the activation of a radical cascade leading to peroxynitrite (ONOO-) accumulation and neuronal death is implicated in Parkinson’s disease (PD). In this regard, tyrosine nitration was found in Lewy bodies (the pathological hallmark of PD and nNOS overexpression was detected in the brain and neutrophils of the PD patients. As nitric oxide (·NO) reacts with quinols to yield semiquinone and nitroxyl anion (NO-), we propose that a similar reaction takes place with 6-OHDA and other cathecol derivatives (collectively referred as QH2 that concentrate in the susbtancia nigra. The kinetics of anaerobic electrochemically measured. ·NO decay with increasing amounts of 6-OHDA, fitted to a second order kinetic model with a rate constant at pH 7 of k=146 M-1 s-1 . This reaction rate increased at basic pH, with an inflexion point at pH 7.5-8 showing an apparent k= 1500 M-1 s-1 . The addition of a pulse of 50 mM ·NO to 50 mM 6- OHDA produced a change in the UV spectrum compatible with the oxidized species (quinone (Q)), being d[Q]/dt linearly related to  ·NO concentration (r=0.99). In accord, the oxidation rate of related cathecols like L-dopa, L-dopamine and L-epinephrine was also increased by ·NO exposure. The formation of ONOO- as a reaction product was tested by 30 min incubation of bovine seroalbumin (BSA) with 300 mM ·NO and 10-25 mM 6-OHDA. The mixtures were subjected to Western blot for the detection of nitrotyrosine Nitration of BSA was dose-dependently enhanced and 20 mM SOD partially prevented it. Collectively, these results suggest the following reactions: 1) QH2 + ·NO  ®       Q·- + NO-