Developmental and Activity-Dependent Expression of LanCL1 Confers Antioxidant Activity Required for Neuronal Survival

• DOI: 10.1016/j.devcel.2014.06.011
• Publication Date: 2014-08-25T15:47:13Z
• Authors: Chao Huang; Mina Chen; Dejiang Pang; Dandan Bi; Yi Zou; Xiaoqiang Xia; Weiwei Yang; Liping Luo; Rongkang Deng; Honglin Tan; Liang Zhou; Shouyang Yu; Liheng Guo; XiaoXia Du; Yiyuan Cui; Jiahua Hu; Qing Mao; Paul F. Worley; Bo Xiao
• Keywords: Neurons; 0301 basic medicine; Brain; Gene Expression Regulation, Developmental; Apoptosis; Mitochondria; Receptors, G-Protein-Coupled; Mice, Inbred C57BL; Mice; Oxidative Stress; 03 medical and health sciences; Animals; Reactive Oxygen Species; Gene Deletion; Developmental Biology

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.