Oxidative Modification of Ferritin Induced by Salsolinol, Catechol Neurotoxin

Abstract

Previous evidences suggest that oxidative alteration of ferritin has been linked to the pathogenesis of Parkinson disease (PD). We have investigated the modification of ferritin induced by salsolinol (SAL), endogenous neurotoxin. When ferritin was incubated with SAL, the aggregation of protein increased with the SAL concentration. SAL also led to the release of iron from ferritin in a SAL concentration-dependent manner. Free radical scavengers and iron specific chelator inhibited the SAL-mediated ferritin modification. Exposure of ferritin to SAL led to the generation of protein carbonyl compounds and the formation of dityrosine. The present results indicate that free radicals may play a role in the modification and iron releasing of ferritin by SAL. It is suggested that oxidative damage of ferritin by SAL might induce the increase of iron content in cells and subsequently led to the deleterious condition. This mechanism, in part, may provide an explanation for the deterioration of organs under neurodegenerative disorder such as PD.