Ischemic Preconditioning Mediates Cyclooxygenase-2 Expression Via Nuclear Factor-Kappa B Activation in Mixed Cortical Neuronal Cultures

Eun Joo Kim, Ami P. Raval, Nina Hirsch, Miguel A. Perez-Pinzon

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Nuclear factor-kappaB (NF-κB) activation occurs following ischemic preconditioning (IPC) in brain. However, the upstream signaling messengers and down-stream targets of NF-κB required for induction of IPC remain undefined. In a previous study, we demonstrated that epsilon protein kinase c (εPKC) was a key mediator of IPC in brain. Activation of εPKC induced cyclooygenase-2 (COX-2) expression and conferred ischemic tolerance in the neuronal and hippocampal slice models. Here, we hypothesized that IPC-mediated COX-2 expression was mediated by NF-κB. We tested this hypothesis in mixed cortical neuron/astrocyte cell cultures. To simulate IPC or ischemia, cell cultures were exposed to 1 or 4 h of oxygen-glucose deprivation, respectively. Our results demonstrated translocation of p65 and p50 subunits of NF-κB into nucleus following IPC or εPKC activation. NF-κB inhibition with pyrrolidine dithiocarbamate (10 μM) abolished IPC or εPKC activator-mediated neuroprotection indicating that NF-κB activation was involved in ischemic tolerance. In parallel studies, inhibition of either εPKC or the extracellular signal-regulated kinase (ERK 1/2) pathway reduced IPC-induced NF-κB activation. Finally, inhibition of NF-κB blocked IPC-induced COX-2 expression. In conclusion, we demonstrated that IPC-signaling cascade comprises εPKC activation → ERK1/2 activation → NF-κB translocation to nucleus → COX-2 expression resulting in neuroprotection in mixed neuronal culture.

Original languageEnglish (US)
Pages (from-to)40-47
Number of pages8
JournalTranslational stroke research
Volume1
Issue number1
DOIs
StatePublished - 2010

Keywords

  • Cerebral ischemia
  • Epsilon protein kinase C
  • Extracellular signal-regulated kinase (ERK1/2)
  • Ischemic tolerance
  • Mixed cortical neuron/astrocyte cell cultures
  • Neuroprotection

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Cardiology and Cardiovascular Medicine

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