Co-activation of GABA receptors inhibits the JNK3 apoptotic pathway via the disassembly of the GluR6-PSD95-MLK3 signaling module in cerebral ischemic-reperfusion

Dong Han; Quanguang Zhang; Yong-Liu; Chong Li; Yan Yan Zong; Chang Zhou Yu; Wei Wang; Jing Zhi Yan; Guang Yi Zhang

doi:10.1016/j.febslet.2008.02.044

Co-activation of GABA receptors inhibits the JNK3 apoptotic pathway via the disassembly of the GluR6-PSD95-MLK3 signaling module in cerebral ischemic-reperfusion

Dong Han, Quanguang Zhang, Yong-Liu, Chong Li, Yan Yan Zong, Chang Zhou Yu, Wei Wang, Jing Zhi Yan, Guang Yi Zhang

Neuroscience and Regenerative Medicine

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1298-1306
Number of pages	9
Journal	FEBS Letters
Volume	582
Issue number	9
DOIs	https://doi.org/10.1016/j.febslet.2008.02.044
State	Published - Apr 16 2008

Keywords

Baclofen
Cerebral ischemia
JNK pathway
Muscimol
Neuroprotection

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2008.02.044

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title = "Co-activation of GABA receptors inhibits the JNK3 apoptotic pathway via the disassembly of the GluR6-PSD95-MLK3 signaling module in cerebral ischemic-reperfusion",

abstract = "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.",

keywords = "Baclofen, Cerebral ischemia, JNK pathway, Muscimol, Neuroprotection",

author = "Dong Han and Quanguang Zhang and Yong-Liu and Chong Li and Zong, {Yan Yan} and Yu, {Chang Zhou} and Wei Wang and Yan, {Jing Zhi} and Zhang, {Guang Yi}",

note = "Funding Information: This work was supported by grants from the Grant research Project of the National Natural Science Foundation of China (No. 90608015); The Key Project of the National Natural Science Foundation of China (No. 30330190); and Education Departmental Nature Science Research Funds of Jiangsu Province of China (06KJB180116 and 07KJA18030). ",

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doi = "10.1016/j.febslet.2008.02.044",

language = "English (US)",

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T1 - Co-activation of GABA receptors inhibits the JNK3 apoptotic pathway via the disassembly of the GluR6-PSD95-MLK3 signaling module in cerebral ischemic-reperfusion

AU - Han, Dong

AU - Zhang, Quanguang

AU - Yong-Liu,

AU - Li, Chong

AU - Zong, Yan Yan

AU - Yu, Chang Zhou

AU - Wang, Wei

AU - Yan, Jing Zhi

AU - Zhang, Guang Yi

N1 - Funding Information: This work was supported by grants from the Grant research Project of the National Natural Science Foundation of China (No. 90608015); The Key Project of the National Natural Science Foundation of China (No. 30330190); and Education Departmental Nature Science Research Funds of Jiangsu Province of China (06KJB180116 and 07KJA18030).

PY - 2008/4/16

Y1 - 2008/4/16

N2 - 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.

AB - 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.

KW - Baclofen

KW - Cerebral ischemia

KW - JNK pathway

KW - Muscimol

KW - Neuroprotection

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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

Abstract

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