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Protein kinase Cdelta is associated with 14-3-3 phosphorylation in seizure-induced neuronal death

Yoon Sook Kim1, Mee Young Choi, Young Hee Kim

  • 1Department of Anatomy and Neurobiology, School of Medicine, Institute of Health Science, Gyeongsang National University, Chilam-dong 92, Jinju, Gyeongnam 660-751, South Korea.

Epilepsy Research
|September 4, 2010
PubMed

Insights

Seizures damage the brain by activating Protein Kinase Cdelta (PKCδ) and phospho-14-3-3 proteins, leading to neuronal death. Targeting these pathways may protect against seizure-induced brain injury.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Epilepsy Research

Background:

  • Prolonged seizures, or status epilepticus, can cause irreversible brain damage and contribute to epilepsy pathogenesis.
  • Protein kinase Cdelta (PKCδ) is implicated in cell death signaling, while 14-3-3 proteins are involved in cell survival pathways by sequestering pro-apoptotic proteins.

Purpose of the Study:

  • To investigate the association between PKCδ, 14-3-3 proteins, and neuronal death in the hippocampus following seizure induction.
  • To explore the molecular mechanisms underlying seizure-induced neuronal injury.

Main Methods:

  • Status epilepticus was induced in a mouse model using systemic kainic acid.
  • Hippocampal tissue was analyzed for levels of cleaved PKCδ, cleaved caspase-3, and phospho-14-3-3ζ (Ser58) using immunohistochemistry and Western blotting.
  • Protein-protein interactions were assessed via co-immunoprecipitation and double immunofluorescence.
  • Neuronal death was quantified using Fluoro-Jade B and active caspase-3 staining, and TUNEL assays.

Main Results:

  • Kainic acid-induced seizures increased cleaved PKCδ, cleaved caspase-3, and phospho-14-3-3ζ (Ser58) in the hippocampus, correlating with significant neuronal cell death.
  • PKCδ was found to interact with 14-3-3 proteins, and this interaction was significantly enhanced post-seizure.
  • Enhanced PKCδ-14-3-3 interaction paralleled increased interaction between Bad and Bcl-x(L), and phospho-14-3-3ζ (Ser58) was upregulated in TUNEL-positive cells.

Conclusions:

  • PKCδ and phospho-14-3-3 are associated with apoptotic neuronal death in the hippocampus after seizures.
  • Modulating PKCδ or phospho-14-3-3 activity may offer a protective strategy against seizure-induced neuronal injury.

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