title: GluR3B Ab's induced oligodendrocyte precursor cells excitotoxicity via mitochondrial dysfunction.
abstract: Studies have indicated that glutamate receptor subunit 3 peptide B antibodies (GluR3B Ab's) by directing against a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype glutamate receptors (AMPARs) subunit 3 (GluR3B) was involved in the hippocampal neuron damage in the pathogenesis of epilepsy. Glutamate accumulation is critical for oligodendrocyte precursors (OPCs) excitotoxic injury. However, remarkably little is known about whether GluR3B Ab's causes OPCs excitotoxicity, and the underlying mechanisms remain unclear. In this study, we found that the survival rate of OPCs decreased, apoptosis increased and the release of LDH increased with GluR3B Ab's treatment. GluR3B Ab's enhanced the level of intracellular Ca2+and reactive oxygen species (ROS), caused mitochondrial potential collapse measured by JC-1 and promoted mitochondrial cytochrome C release. AMPARs antagonist NBQX reversed OPCs apoptosis caused by GluR3B Ab's. Taken together, these data suggests that AMPAR was involved in GluR3B Ab's-induced OPCs toxicity by mitochondrial dysfunction. The study revealed a new mechanism for OPCs excitotoxicity in many central nervous system diseases such as epilepsy.
authors.affiliation: Department of Cell Biology and Neurobiology, Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cell Biology and Neurobiology, Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cell Biology and Neurobiology, Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, PR China.
authors.forename: Wan Tong
authors.initials: WT
authors.lastname: Du
authors.affiliation: Department of Cell Biology and Neurobiology, Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, PR China.
authors.forename: Xiu Xiang
authors.initials: XX
authors.lastname: Wu
authors.affiliation: Department of Cell Biology and Neurobiology, Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, PR China.
authors.forename: Fu Xing
authors.initials: FX
authors.lastname: Dong
authors.affiliation: Department of Cell Biology and Neurobiology, Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, PR China.
authors.forename: Xue Bin
authors.initials: XB
authors.lastname: Qu
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou, 221002, Jiangsu, PR China. Electronic address: fandoc@163.com.
authors.forename: Hong Bin
authors.initials: HB
authors.lastname: Fan
authors.affiliation: Department of Cell Biology and Neurobiology, Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, PR China. Electronic address: wenxi_yao@163.com.
authors.forename: Rui Qin
authors.initials: RQ
authors.lastname: Yao
mesh_terms: D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D008928:Mitochondria / Q000276:immunology* / Q000378:metabolism; D000073637:Oligodendrocyte Precursor Cells / Q000276:immunology* / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D018091:Receptors, AMPA / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D017382:Reactive Oxygen Species; D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3; D002118:Calcium
keywords: Excitotoxicity; Glutamate receptor antibody; Mitochondria; Oligodendrocyte precursor cells