title: Oxidative modification of neurofilament-L by copper-catalyzed reaction.
abstract: Neurofilament-L (NF-L) is a major element of neuronal cytoskeletons and known to be important for neuronal survival in vivo. Since oxidative stress might play a critical role in the pathogenesis of neurodegenerative diseases, we investigated the role of copper and peroxide in the modification of NF-L. When disassembled NF-L was incubated with copper ion and hydrogen peroxide, then the aggregation of protein was proportional to copper and hydrogen peroxide concentrations. Dityrosine crosslink formation was obtained in copper-mediated NF-L aggregates. The copper-mediated modification of NF-L was significantly inhibited by thiol antioxidants, Nacetylcysteine, glutathione, and thiourea. A thioflavin-T binding assay was performed to determine whether the copper/H2O2 system-induced in vitro aggregation of NF-L displays amyloid-like characteristics. The aggregate of NF-L displayed thioflavin T reactivity, which was reminiscent of amyloid. This study suggests that copper-mediated NF-L modification might be closely related to oxidative reactions which may play a critical role in neurodegenerative diseases.
authors.affiliation: Department of Genetic Engineering, Chongju University, Chongju 360-764, Korea.
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Kim
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Kang
mesh_terms: D000682:Amyloid / Q000378:metabolism; D000818:Animals; D003300:Copper / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D051379:Mice; D016900:Neurofilament Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D013050:Spectrometry, Fluorescence
chemical_list: D000682:Amyloid; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D003300:Copper