title: Hydrogen peroxide mediated the neurotoxicity of an antibody against plasmalemmal neuronspecific enolase in primary cortical neurons.
abstract: Neuron-specific enolase (NSE) is not only a glycolytic enzyme in the cytosol, but also localized in the synaptic plasma membrane. The plasmalemmal NSE is one of autoantigen targets in post-streptococcal autoimmune central nervous system disease. Although anti-neuronal antibodies in patients bind to a restricted group of NSE in cerebral cortex, it has not yet been clarified how the anti-NSE antibody have negative impacts on cortical neurons. Here, we found that NSE was also localized at neuronal cell bodies and neuritis on the neuronal cell surface in the primary culture of rat cortical neurons. The anti-NSE antibody induced neuronal cell death in a concentration-dependent manner. The neuronal cell death required a lag time and was not accompanied with caspase-3 activation and chromatin condensation. The anti-NSE antibody elevated a level of intracellular H2O2 prior to neuronal cell death. Catalase protected neurons from the anti-NSE antibody-induced H2O2 generation and cell death. The post-treatment of neurons with catalase after the application of the anti-NSE antibody exhibited neuroprotective effects as well as the co-treatment. The cascade of mitogen-activated protein kinase (MAPK) is one of signal transductions of H2O2. Among MAPK, a c-Jun N-terminal kinase partially contributed to the neurotoxicity of anti-NSE antibody. Thus, the anti-NSE antibody acted at the plasmalemmal NSE, produced H2O2, and caused neuronal cell death via non-apoptotic pathway in the cortical neurons.
authors.affiliation: Division of Physiology, Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, kami-ohno 7-Chome, Himeji, Hyogo 670-8524, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Division of Physiology, Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, kami-ohno 7-Chome, Himeji, Hyogo 670-8524, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Koma
authors.affiliation: Division of Physiology, Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, kami-ohno 7-Chome, Himeji, Hyogo 670-8524, Japan. Electronic address: yagami@himeji-du.ac.jp.
authors.forename: Tatsurou
authors.initials: T
authors.lastname: Yagami
mesh_terms: D000818:Animals; D000906:Antibodies / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002458:Cell Fractionation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000276:immunology*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: C477819:15-deoxyprostaglandin J2; D000906:Antibodies; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D006861:Hydrogen Peroxide; D002374:Catalase; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase; D015230:Prostaglandin D2
keywords: Catalase; Hydrogen peroxide; Neuron-specific enolase; Post-streptococcal autoimmune disorders; Trans-plasma-membrane oxidoreductase; c-Jun N-terminal kinase