title: Oxidative modification of neurofilament-L by the Cu,Zn-superoxide dismutase and hydrogen peroxide system.
abstract: Neurofilament-L (NF-L) is a major element of neuronal cytoskeletons and known to be important for their survival in vivo. Since oxidative stress might play a critical role in the pathogenesis of neurodegenerative diseases, we investigated the role of Cu,Zn-superoxide dismutase (SOD) in the modification of NF-L. When disassembled NF-L was incubated with Cu,Zn-SOD and H2O2, the aggregation of protein was proportional to the concentration of hydrogen peroxide. Cu,Zn-SOD/H2O2-mediated modification of NF-L was significantly inhibited by radical scavenger, spin trap agents and copper chelators. Dityrosine crosslink formation was obtained in Cu,Zn-SOD/H2O2-mediated NF-L aggregates. Antioxidant molecules, carnosine and anserine significantly inhibited the aggregation of NF-L and the formation of dityrosine. This study suggests that copper-mediated NF-L modification may be closely related to oxidative reactions which play a critical role in neurodegenerative diseases.
authors.affiliation: Department of Genetic Engineering, Cheongju University, Cheongju 360-764, Korea.
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Kim
authors.forename: Moon Sik
authors.initials: MS
authors.lastname: Jeong
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Jung
authors.initials: J
authors.lastname: Hoon Kang
mesh_terms: D000818:Animals; D000861:Anserine / Q000378:metabolism; D002336:Carnosine / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051379:Mice; D019636:Neurodegenerative Diseases / Q000378:metabolism; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
chemical_list: D016900:Neurofilament Proteins; C044882:neurofilament protein L; D003300:Copper; D002336:Carnosine; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000861:Anserine; D015032:Zinc