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

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, Xiao Xia Du, Yiyuan Cui, Jiahua Hu, Qing Mao, Paul F. Worley, Bo Xiao

Research output: Contribution to journalArticle

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. Itsexpression 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.

Original languageEnglish (US)
Pages (from-to)479-487
Number of pages9
JournalDevelopmental Cell
Volume30
Issue number4
DOIs
StatePublished - Aug 25 2014

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ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Cite this

Huang, C., Chen, M., Pang, D., Bi, D., Zou, Y., Xia, X., Yang, W., Luo, L., Deng, R., Tan, H., Zhou, L., Yu, S., Guo, L., Du, X. X., Cui, Y., Hu, J., Mao, Q., Worley, P. F., & Xiao, B. (2014). Developmental and Activity-Dependent Expression of LanCL1 Confers Antioxidant Activity Required for Neuronal Survival. Developmental Cell, 30(4), 479-487. https://doi.org/10.1016/j.devcel.2014.06.011