Oxidative modification of neurofilament-L by the Cu,Zn-superoxide dismutase and hydrogen peroxide system.
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.
Kim
Nam Hoon
NH
Department of Genetic Engineering, Cheongju University, Cheongju 360-764, Korea.
Jeong
Moon Sik
MS
Choi
Soo Young
SY
Hoon Kang
Jung
J
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
D016900:Neurofilament Proteins; C044882:neurofilament protein L; D003300:Copper; D002336:Carnosine; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000861:Anserine; D015032:Zinc