Author(s): Kim YS, Choi MY, Kim YH, Jeon BT, Lee DH,
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Abstract Prolonged seizures cause significant damage to the brain, and cellular damage due to status epilepticus may be related to the pathogenesis of epilepsy. Protein kinase Cdelta (PKCδ) mediates multiple cell death signalings, and 14-3-3 proteins regulate survival pathways in brain, sequestering certain pro-apoptotic proteins. Presently, we examined the association between PKCδ and 14-3-3 with seizure-induced neuronal death using mouse model. Status epilepticus was induced by systemic kainic acid. Kainate-induced seizures caused an increase in levels of cleaved PKCδ in the hippocampus, along with up-regulation of cleaved caspase-3 and phospho-14-3-3ζ (Ser58), as well as extensive hippocampal cell death as visualized with Fluoro-Jade B and anti-active caspase-3 staining. Furthermore, co-immunoprecipitation or double immunofluorescence analysis revealed that PKCδ interacts with 14-3-3, and interaction between PKCδ and 14-3-3 was significantly enhanced in the hippocampus after seizures, paralleling increased interaction between Bad and Bcl-x(L). Moreover, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells had upregulated phospho-14-3-3ζ (Ser58) in the hippocampus after seizures. These findings suggest that PKCδ and phospho-14-3-3 are associated with apoptotic cell death in the hippocampus after seizures, and targeting PKCδ or phospho-14-3-3 may be potently protective against seizure-induced neuronal injury. Copyright © 2010 Elsevier B.V. All rights reserved.
This article was published in Epilepsy Res
and referenced in Journal of Proteomics & Bioinformatics