Ischemia activates JNK/c-Jun/AP-1 pathway to up-regulate 14-3-3gamma in astrocyte.
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 14-3-3gamma 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 14-3-3gamma 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 14-3-3gamma 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 14-3-3gamma up-regulation indicating that ischemia-induced up-regulation of 14-3-3gamma in astrocyte involves activation of the JNK/p-c-Jun/AP-1 pathway.
Dong
Yan
Y
Department of Neurobiology, School of Basic Medical Sciences, Neuroscience Research Institute, the Key Laboratory for Neuroscience (Ministry of Education), Peking University, Beijing, China.
Liu
Hua Dong
HD
Zhao
Rui
R
Yang
Chun Zhang
CZ
Chen
Xiao Qian
XQ
Wang
Xin Hong
XH
Lau
Lok Ting
LT
Chen
Jianguo
J
Yu
Albert Cheung Hoi
AC
D048948:14-3-3 Proteins / Q000096:biosynthesis*; D001253:Astrocytes / Q000201:enzymology / Q000378:metabolism*; D001273:Atmosphere Exposure Chambers; D002545:Brain Ischemia / Q000201:enzymology / Q000378:metabolism*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015854:Up-Regulation
D048948:14-3-3 Proteins; D004791:Enzyme Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D012313:RNA; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases