title: Oxidative modification of neurofilament-L and neuronal cell death induced by the catechol neurotoxin, tetrahydropapaveroline.
abstract: Tetrahydropapaveroline (THP), which is an endogenous neurotoxin, has been suspected to be associated with dopaminergic neurotoxicity of l-DOPA. In this study, we examined oxidative modification of neurofilament-L (NF-L) and neuronal cell death induced by THP. When disassembled NF-L was incubated with THP, protein aggregation was increased in a time- and THP dose-dependent manner. The formation of carbonyl compounds and dityrosine were observed in the THP-mediated NF-L aggregates. Radical scavengers reduced THP-mediated NF-L modification. These results suggest that the modification of NF-L by THP may be due to oxidative damage resulting from the generation of reactive oxygen species (ROS). When THP exposed NF-L was subjected to amino acid analysis, glutamate, proline and lysine residues were found to be particularly sensitive. We also investigated the effects of copper ions on THP-mediated NF-L modification. At a low concentration of THP, copper ions enhanced the modification of NF-L. Treatment of C6 astrocyte cells with THP led to a concentration-dependent reduction in cell viability. When these cells were treated with 100μM THP, the levels of ROS increased 3.5-fold compared with control cells. Furthermore, treatment of cells with THP increased NF-L aggregate formation, suggesting the involvement of NF-L modification in THP-induced cell damage.
authors.affiliation: Department of Genetic Engineering, Cheongju University, Cheongju 360-764, South Korea.
authors.forename: Inn Goo
authors.initials: IG
authors.lastname: Kyeong
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Kang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002396:Catechols / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D016166:Free Radical Scavengers / Q000494:pharmacology; D051379:Mice; D008970:Molecular Weight; D019636:Neurodegenerative Diseases / Q000378:metabolism; D016900:Neurofilament Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D013765:Tetrahydropapaveroline / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002396:Catechols; D016166:Free Radical Scavengers; D016900:Neurofilament Proteins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C044882:neurofilament protein L; D013765:Tetrahydropapaveroline; D003300:Copper