title: Ischemia preconditioning protects astrocytes from ischemic injury through 14-3-3γ.
abstract: Stroke is a leading cause of death and disability, and new strategies are required to reduce neuronal injury and improve prognosis. Ischemia preconditioning (IPC) is an intrinsic phenomenon that protects cells from subsequent ischemic injury and might provide promising mechanisms for clinical treatment. In this study, primary astrocytes exhibited significantly less cell death than control when exposed to different durations of IPC (15, 30, 60, or 120 min). A 15-min duration was the most effective IPC to protect astrocytes from 8-hr-ischemia injury. The protective mechanisms of IPC involve the upregulation of protective proteins, including 14-3-3γ, and attenuation of malondialdehyde (MDA) content and ATP depletion. 14-3-3γ is an antiapoptotic intracellular protein that was significantly upregulated for up to 84 hr after IPC. In addition, IPC promoted activation of the c-Jun N-terminal kinase (JNK), extracellular signal-related kinase (ERK)-1/2, p38, and protein kinase B (Akt) signaling pathways. When JNK was specifically inhibited with SP600125, the upregulation of 14-3-3γ induced by IPC was almost completely abolished; however, there was no effect on ATP or MDA levels. This suggests that, even though both energy preservation and 14-3-3γ up-regulation were turned on by IPC, they were controlled by different pathways. The ERK1/2, p38, and Akt signaling pathways were not involved in the 14-3-3γ upregulation and energy preservation. These results indicate that IPC could protect astrocytes from ischemia injury by inducing 14-3-3γ and by alleviating energy depletion through different pathways, suggesting multiple protection of IPC and providing new insights into potential stroke therapies.
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China.
authors.forename: Chao Rui
authors.initials: CR
authors.lastname: Chai
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China.
authors.forename: Xi Hua
authors.initials: XH
authors.lastname: Jia
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China.
authors.forename: Jin Ge
authors.initials: JG
authors.lastname: Kong
authors.affiliation: Department of Pathophysiology, Ministry of Education and Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiao Qian
authors.initials: XQ
authors.lastname: Chen
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China.
authors.forename: Greg
authors.initials: G
authors.lastname: Vatcher
authors.affiliation: Key Laboratory of Biomembrane and Membrane Bioengineering, Key Laboratory of Cell Proliferation and Differentiation, Ministry of Education, College of Life Sciences, Peking University, Beijing, China.
authors.forename: Jian Guo
authors.initials: JG
authors.lastname: Chen
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, China.|Department of Neurobiology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China.|Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China.|Laboratory of Translational Medicine, Institute of Systems Biomedicine, Peking University, Beijing, China.
authors.forename: Albert Cheung Hoi
authors.initials: AC
authors.lastname: Yu
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism*; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007511:Ischemia / Q000517:prevention & control; D019194:Ischemic Preconditioning; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D048948:14-3-3 Proteins; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase
keywords: 14-3-3γ; ATP; JNK; astrocytes; ischemia preconditioning