Neuroprotection of co-activation of GABA receptors by preventing caspase-3 denitrosylation in KA-induced seizures

Xue Wen Wei, Hui Yan, Bo Xu, Yong Ping Wu, Chong Li, Guang Yi Zhang

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Previous studies have demonstrated that kainic acid (KA)-induced seizures can cause the enhancement of excitation and lead to neuronal death in rat hippocampus. Co-activation 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 induced by KA in epileptic rat hippocampal CA1 and CA3 regions. Caspase-3 is a cysteine protease located in both the cytoplasm and mitochondrial intermembrane space that is a central effector of many apoptotic pathways. We designed experiments to elucidate the underlying molecular mechanisms of procaspase-3 activation and neuroprotection of co-activation of GABA receptors against neuronal death induced by KA. In this study, we show that co-activation of GABA receptors can attenuate the Fas/FasL apoptotic signaling pathway and inhibit the increased of thioredoxin reductase activity induced by KA, subsequently inhibit the activation of procaspase-3 by diminishing the denitrosylation of its active-site thiol and decreasing the cleavage of the caspase-3 zymogen to its active subunits. These results indicate that co-activation of GABA receptors results in neuroprotection by preventing caspase-3 denitrosylation in KA-induced seizure of rats.

Original languageEnglish (US)
Pages (from-to)617-623
Number of pages7
JournalBrain Research Bulletin
Volume88
Issue number6
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

Keywords

  • Caspase-3
  • Denitrosylation
  • Fas/FasL
  • GABA receptor
  • Kainic acid
  • Seizure

ASJC Scopus subject areas

  • Neuroscience(all)

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