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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1298-1306
Number of pages9
JournalFEBS Letters
Volume582
Issue number9
DOIs
StatePublished - Apr 16 2008

Fingerprint

GABA Receptors
Brain Ischemia
Reperfusion
Chemical activation
GABA-B Receptors
GABA-A Receptor Agonists
Muscimol
Baclofen
Butyric Acid
gamma-Aminobutyric Acid
Glutamic Acid
Oxygen
Glucose

Keywords

  • Baclofen
  • Cerebral ischemia
  • JNK pathway
  • Muscimol
  • Neuroprotection

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Co-activation of GABA receptors inhibits the JNK3 apoptotic pathway via the disassembly of the GluR6-PSD95-MLK3 signaling module in cerebral ischemic-reperfusion. / Han, Dong; Zhang, Quanguang; Yong-Liu; Li, Chong; Zong, Yan Yan; Yu, Chang Zhou; Wang, Wei; Yan, Jing Zhi; Zhang, Guang Yi.

In: FEBS Letters, Vol. 582, No. 9, 16.04.2008, p. 1298-1306.

Research output: Contribution to journalArticle

Han, Dong ; Zhang, Quanguang ; Yong-Liu ; Li, Chong ; Zong, Yan Yan ; Yu, Chang Zhou ; Wang, Wei ; Yan, Jing Zhi ; Zhang, Guang Yi. / Co-activation of GABA receptors inhibits the JNK3 apoptotic pathway via the disassembly of the GluR6-PSD95-MLK3 signaling module in cerebral ischemic-reperfusion. In: FEBS Letters. 2008 ; Vol. 582, No. 9. pp. 1298-1306.
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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.",
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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

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