Oxidative Modification of Neurofilament-L by the Cytochrome c and Hydrogen Peroxide System

As neurofilament proteins are major cytoskeletal components of neuron, abnormality of neurofilament is proposed in brain with neurodegenerative disorders such as Parkinson's disease (PD). Since oxidative stress might play a critical role in altering normal brain proteins, we investigated the oxidative modification of neurofilament-L (NF-L) induced by the reaction of cytochrome c with H₂O₂. When NF-L was incubated with cytochrome c and H₂O₂, the protein aggregation was increased in cytochrome c and H₂O₂ concentrationsdependent manner. Radical scavengers, azide, formate and N-acetyl cysteine, prevented the aggregation of NFL induced by the cytochrome c/H₂O₂ system. The formations of carbonyl group and dityrosine were obtained in cytochrome c/H₂O₂-mediated NF-L aggregates. Iron specific chelator, desferoxamine, prevented the cytochrome c/H₂O₂ system-mediated NF-L aggregation. These results suggest that the cytochrome c/H₂O₂ system may be related to abnormal aggregation of NF-L which may be involved in the pathogenesis of PD and related disorders