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

doi:10.1016/j.devcel.2014.06.011

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

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 language	English (US)
Pages (from-to)	479-487
Number of pages	9
Journal	Developmental Cell
Volume	30
Issue number	4
DOIs	https://doi.org/10.1016/j.devcel.2014.06.011
State	Published - Aug 25 2014

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

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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

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, XX, Cui, Y, Hu, J, Mao, Q, Worley, PF & Xiao, B 2014, 'Developmental and Activity-Dependent Expression of LanCL1 Confers Antioxidant Activity Required for Neuronal Survival', Developmental Cell, vol. 30, no. 4, pp. 479-487. https://doi.org/10.1016/j.devcel.2014.06.011

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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. 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.",

author = "Chao Huang and Mina Chen and Dejiang Pang and Dandan Bi and Yi Zou and Xiaoqiang Xia and Weiwei Yang and Liping Luo and Rongkang Deng and Honglin Tan and Liang Zhou and Shouyang Yu and Liheng Guo and Du, {Xiao Xia} and Yiyuan Cui and Jiahua Hu and Qing Mao and Worley, {Paul F.} and Bo Xiao",

note = "Funding Information: M.C., L.Z., Y.C., and Y.Z. generated LanCL1 mouse models with the help of the Transgenic Facility of Johns Hopkins University. This work was supported by grants from National 973 Basic Research Program of China (2009CB941400 to B.X.) and the NIH (5P50DA000266-42 to P.F.W.), and in part by the National Basic Research Program of China (No. 2010CB529900) and the National Natural Science Foundation of China (No. 81123003). ",

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doi = "10.1016/j.devcel.2014.06.011",

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AU - Huang, Chao

AU - Chen, Mina

AU - Pang, Dejiang

AU - Bi, Dandan

AU - Zou, Yi

AU - Xia, Xiaoqiang

AU - Yang, Weiwei

AU - Luo, Liping

AU - Deng, Rongkang

AU - Tan, Honglin

AU - Zhou, Liang

AU - Yu, Shouyang

AU - Guo, Liheng

AU - Du, Xiao Xia

AU - Cui, Yiyuan

AU - Hu, Jiahua

AU - Mao, Qing

AU - Worley, Paul F.

AU - Xiao, Bo

N1 - Funding Information: M.C., L.Z., Y.C., and Y.Z. generated LanCL1 mouse models with the help of the Transgenic Facility of Johns Hopkins University. This work was supported by grants from National 973 Basic Research Program of China (2009CB941400 to B.X.) and the NIH (5P50DA000266-42 to P.F.W.), and in part by the National Basic Research Program of China (No. 2010CB529900) and the National Natural Science Foundation of China (No. 81123003).

PY - 2014/8/25

Y1 - 2014/8/25

N2 - 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.

AB - 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.

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

Abstract

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