Ca2+/calmodulin-dependent protein kinase ii contributes to hypoxic ischemic cell death in neonatal hippocampal slice cultures

Qing Lu, Valerie A. Harris, Xutong Sun, Yali Hou, Stephen M. Black

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We have recently shown that p38MAP kinase (p38MAPK) stimulates ROS generation via the activation of NADPH oxidase during neonatal hypoxia-ischemia (HI) brain injury. However, how p38MAPK is activated during HI remains unresolved and was the focus of this study. Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a key role in brain synapse development, neural transduction and synaptic plasticity. Here we show that CaMKII activity is stimulated in rat hippocampal slice culture exposed to oxygen glucose deprivation (OGD) to mimic the condition of HI. Further, the elevation of CaMKII activity, correlated with enhanced p38MAPK activity, increased superoxide generation from NADPH oxidase as well as necrotic and apoptotic cell death. All of these events were prevented when CaMKII activity was inhibited with KN93. In a neonatal rat model of HI, KN93 also reduced brain injury. Our results suggest that CaMKII activation contributes to the oxidative stress associated with neural cell death after HI.

Original languageEnglish (US)
Article numbere70750
JournalPLoS One
Volume8
Issue number8
DOIs
StatePublished - Aug 19 2013

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Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Cell death
ischemia
Cell culture
cell death
hypoxia
calmodulin
Cell Death
Ischemia
protein kinases
Brain
phosphotransferases (kinases)
Neuronal Plasticity
Phosphotransferases
NADPH Oxidase
brain
Brain Injuries
Rats
Chemical activation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Ca2+/calmodulin-dependent protein kinase ii contributes to hypoxic ischemic cell death in neonatal hippocampal slice cultures. / Lu, Qing; Harris, Valerie A.; Sun, Xutong; Hou, Yali; Black, Stephen M.

In: PLoS One, Vol. 8, No. 8, e70750, 19.08.2013.

Research output: Contribution to journalArticle

Lu, Qing ; Harris, Valerie A. ; Sun, Xutong ; Hou, Yali ; Black, Stephen M. / Ca2+/calmodulin-dependent protein kinase ii contributes to hypoxic ischemic cell death in neonatal hippocampal slice cultures. In: PLoS One. 2013 ; Vol. 8, No. 8.
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