|
|||||
|
|
Ischemia activates JNK/c-Jun/AP-1 pathway to up-regulate 14-3-3γ in astrocyte |
|
| Authors: | Yan Dong Hua Dong Liu Rui Zhao Chun Zhang Yang Xiao Qian Chen† Xin Hong Wang Lok Ting Lau‡ Jianguo Chen§ Albert Cheung Hoi Yu |
| Institution: | 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; Department of Pathophysiology and Key Laboratory of Neurological Diseases of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hai Kang Life Corporation Limited, Beijing, China; 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 |
| 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. |
| Keywords: | AP-1 astrocytes c-Jun JNK ischemia 14-3-3γ |