title: Developmental and activity-dependent expression of LanCL1 confers antioxidant activity required for neuronal survival.
abstract: Production of reactive oxygen species (ROS) increases with neuronal activity that accompanies synaptic development and function. Transcription-related factors and metabolic enzymes that are expressed in all tissues have been described to counteract neuronal ROS to prevent oxidative damage. Here, we describe the antioxidant gene LanCL1 that is prominently enriched in brain neurons. Its expression is developmentally regulated and induced by neuronal activity, neurotrophic factors implicated in neuronal plasticity and survival, and oxidative stress. Genetic deletion of LanCL1 causes enhanced accumulation of ROS in brain, as well as development-related lipid, protein, and DNA damage; mitochondrial dysfunction; and apoptotic neurodegeneration. LanCL1 transgene protects neurons from ROS. LanCL1 protein purified from eukaryotic cells catalyzes the formation of thioether products similar to glutathione S-transferase. These studies reveal a neuron-specific glutathione defense mechanism that is essential for neuronal function and survival.
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Mina
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Dejiang
authors.initials: D
authors.lastname: Pang
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Dandan
authors.initials: D
authors.lastname: Bi
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Xia
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Luo
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Rongkang
authors.initials: R
authors.lastname: Deng
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Tan
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Shouyang
authors.initials: S
authors.lastname: Yu
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Liheng
authors.initials: L
authors.lastname: Guo
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: XiaoXia
authors.initials: X
authors.lastname: Du
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Yiyuan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jiahua
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, West China Hospital, Chengdu 610041, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Mao
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: pworley@jhmi.edu.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Worley
authors.affiliation: Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurosurgery, West China Hospital, Chengdu 610041, People's Republic of China. Electronic address: bxiao365@yahoo.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: C485882:Lancl1 protein, mouse; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled