Ischemia activates JNK/c-Jun/AP-1 pathway to up-regulate 14-3-3γ in astrocyte

Authors

  • Yan Dong,

    1. Department of Neurobiology, School of Basic Medical Sciences, Neuroscience Research Institute, the Key Laboratory for Neuroscience (Ministry of Education), the Key Laboratory for Neuroscience (Ministry of Public Health), Peking University, Beijing, China
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    • 1

      These authors contributed equally for this study.

  • Hua Dong Liu,

    1. Department of Neurobiology, School of Basic Medical Sciences, Neuroscience Research Institute, the Key Laboratory for Neuroscience (Ministry of Education), the Key Laboratory for Neuroscience (Ministry of Public Health), Peking University, Beijing, China
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    • 1

      These authors contributed equally for this study.

  • Rui Zhao,

    1. Department of Neurobiology, School of Basic Medical Sciences, Neuroscience Research Institute, the Key Laboratory for Neuroscience (Ministry of Education), the Key Laboratory for Neuroscience (Ministry of Public Health), Peking University, Beijing, China
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  • Chun Zhang Yang,

    1. Department of Neurobiology, School of Basic Medical Sciences, Neuroscience Research Institute, the Key Laboratory for Neuroscience (Ministry of Education), the Key Laboratory for Neuroscience (Ministry of Public Health), Peking University, Beijing, China
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  • Xiao Qian Chen,

    1. Department of Pathophysiology and Key Laboratory of Neurological Diseases of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Xin Hong Wang,

    1. Department of Neurobiology, School of Basic Medical Sciences, Neuroscience Research Institute, the Key Laboratory for Neuroscience (Ministry of Education), the Key Laboratory for Neuroscience (Ministry of Public Health), Peking University, Beijing, China
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  • Lok Ting Lau,

    1. Department of Neurobiology, School of Basic Medical Sciences, Neuroscience Research Institute, the Key Laboratory for Neuroscience (Ministry of Education), the Key Laboratory for Neuroscience (Ministry of Public Health), Peking University, Beijing, China
    2. Hai Kang Life Corporation Limited, Beijing, China
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  • Jianguo Chen,

    1. Department of Cell Biology and Genetics, College of Life Sciences, the Key Laboratory of Cell Proliferation and Differentiation (Ministry of Education) and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, Peking University, Beijing, China
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  • Albert Cheung Hoi Yu

    1. Department of Neurobiology, School of Basic Medical Sciences, Neuroscience Research Institute, the Key Laboratory for Neuroscience (Ministry of Education), the Key Laboratory for Neuroscience (Ministry of Public Health), Peking University, Beijing, China
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Address correspondence and reprint requests to Albert Cheung Hoi Yu, Ph.D., Department of Neurobiology, School of Basic Medical Sciences, Neuroscience Research Institute, Peking University, 38 Xue Yuan Road, Peking University Health Science Center, Beijing 100191, China.
E-mail: achy@hsc.pku.edu.cn; achy@haikanglife.com

Abstract

Ischemia occurs in the brain as the result of stroke and other related injuries and few therapies are effective. If more is understood then potential treatments could be investigated. It was previously reported that 14-3-3γ could be up-regulated by ischemia in astrocyte to protect cells from ischemia-induced apoptosis. In this study, we attempted to uncover the mechanism responsible for this 14-3-3γ up-regulation in primary culture of astrocytes under ischemic-like conditions. It was found that in vitro ischemia may activate PI3K/Akt and MAPK signaling pathways. Astrocyte cultures were treated with LY294002 (PI3K inhibitor), U0126 (ERK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor). Only SP600125 could inhibit the ischemia-induced 14-3-3γ up-regulation in astrocytes. At the same time, we observed an ischemia-induced nuclear translocation of p-c-Jun, a major downstream component of JNK. Inhibition of AP-1 with curcumin also inhibited 14-3-3γ up-regulation indicating that ischemia-induced up-regulation of 14-3-3γ in astrocyte involves activation of the JNK/p-c-Jun/AP-1 pathway.

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