The neuroprotective action of SP600125, a new inhibitor of JNK, on transient brain ischemia/reperfusion-induced neuronal death in rat hippocampal CA1 via nuclear and non-nuclear pathways

Qiu Hua Guan, Dong Sheng Pei, Quanguang Zhang, Zhi Bin Hao, Tian Le Xu, Guang Yi Zhang

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Increasing evidence suggests that c-Jun N-terminal kinase (JNK) is an important kinase mediating neuronal apoptosis in brain ischemia. To further study the roles of JNK activation in hippocampal CA1 neurons in a rat model of transient global ischemia, we assessed the effect of JNK inhibition by SP600125 on the degree of brain injury. Our results demonstrated that SP600125 significantly increased the number of surviving cells in hippocampal CA1 subfield and decreased the activation of p-JNK1/2 and p-JNK3 at 30 min and 3 days after brain ischemia. Moreover, SP600125 significantly diminished the increased levels of phosphorylated-c-Jun (Ser63/73) and phosphorylated-Bcl-2 (Ser87) at 3 h after brain ischemia. These results indicate that SP600125, a new inhibitor of JNK, protected transient brain ischemia/reperfusion-induced neuronal death in rat hippocampal CA1 region at least via suppressing the activation of nuclear substrate (c-Jun) and inactivating non-nuclear substrate (Bcl-2) induced by ischemic insult. Thus, inhibiting JNK activity by SP600125 may represent a new and effective strategy to treat ischemic stoke.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalBrain Research
Volume1035
Issue number1
DOIs
StatePublished - Feb 21 2005
Externally publishedYes

Fingerprint

JNK Mitogen-Activated Protein Kinases
Brain Ischemia
Reperfusion
Hippocampal CA1 Region
Brain Injuries
Phosphotransferases
Ischemia
Cell Count
anthra(1,9-cd)pyrazol-6(2H)-one
Apoptosis
Neurons

Keywords

  • Bcl-2
  • Brain ischemia
  • JNK
  • SP600125
  • c-Jun

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

The neuroprotective action of SP600125, a new inhibitor of JNK, on transient brain ischemia/reperfusion-induced neuronal death in rat hippocampal CA1 via nuclear and non-nuclear pathways. / Guan, Qiu Hua; Pei, Dong Sheng; Zhang, Quanguang; Hao, Zhi Bin; Xu, Tian Le; Zhang, Guang Yi.

In: Brain Research, Vol. 1035, No. 1, 21.02.2005, p. 51-59.

Research output: Contribution to journalArticle

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