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Co‐activation of GABA receptors inhibits the JNK3 apoptotic pathway via the disassembly of the GluR6‐PSD95‐MLK3 signaling module in cerebral ischemic‐reperfusion
Author(s) -
Han Dong,
Zhang Quan-Guang,
Li Chong,
Zong Yan-Yan,
Yu Chang-Zhou,
Wang Wei,
Yan Jing-Zhi,
Zhang Guang-Yi
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.02.044
Subject(s) - neuroprotection , inhibitory postsynaptic potential , glutamate receptor , excitatory postsynaptic potential , ischemia , signal transduction , receptor , muscimol , pharmacology , chemistry , microbiology and biotechnology , agonist , biology , neuroscience , biochemistry , medicine
In this study, we investigated whether the increase of inhibitory γ‐amino butyric acid (GABA) signal suppresses the excitatory glutamate signal induced by cerebral ischemia and the underlying mechanisms. In global cerebral ischemia, focal cerebral ischemia and oxygen‐glucose deprivation, application of muscimol and baclofen, agonists of GABA(A) receptor and GABA(B) receptor, exerted neuroprotection. The agonists inhibited the increased assembly of the GluR6‐PSD‐95‐MLK3 module induced by cerebral ischemia and the activation of the MLK3‐MKK4/7‐JNK3 cascade. Our results suggest that stimulation of the inhibitory GABA receptors can attenuate the excitatory JNK3 apoptotic signaling pathway via inhibiting the increased assembly of the GluR6‐PSD‐95‐MLK3 signaling module in cerebral ischemia.