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Dev Cell. 2014 Aug 25;30(4):479-87. doi: 10.1016/j.devcel.2014.06.011.

Developmental and activity-dependent expression of LanCL1 confers antioxidant activity required for neuronal survival.

Author information

1
Neuroscience and Metabolism Research, The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
2
Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, People's Republic of China.
3
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.
4
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
5
Department of Neurosurgery, West China Hospital, Chengdu 610041, People's Republic of China.
6
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: pworley@jhmi.edu.
7
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.

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.

PMID:
25158856
PMCID:
PMC4147379
DOI:
10.1016/j.devcel.2014.06.011
[Indexed for MEDLINE]
Free PMC Article

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