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Ischemia activates JNK/c‐Jun/AP‐1 pathway to up‐regulate 14‐3‐3γ in astrocyte
Author(s) -
Dong Yan,
Liu Hua Dong,
Zhao Rui,
Yang Chun Zhang,
Chen Xiao Qian,
Wang Xin Hong,
Lau Lok Ting,
Chen Jianguo,
Yu Albert Cheung Hoi
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.05974.x
Subject(s) - ly294002 , astrocyte , ischemia , p38 mitogen activated protein kinases , mapk/erk pathway , pi3k/akt/mtor pathway , microbiology and biotechnology , chemistry , pharmacology , brain ischemia , apoptosis , signal transduction , kinase , neuroscience , biology , medicine , biochemistry , central nervous system
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.