title: Protein kinase Cdelta is associated with 14-3-3 phosphorylation in seizure-induced neuronal death.
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.
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Institute of Health Science, Gyeongsang National University, Chilam-dong 92, Jinju, Gyeongnam 660-751, South Korea.
authors.forename: Yoon Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Choi
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Byeong Tak
authors.initials: BT
authors.lastname: Jeon
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Lee
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Gyeong Jae
authors.initials: GJ
authors.lastname: Cho
authors.forename: Wan Sung
authors.initials: WS
authors.lastname: Choi
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology*; D007608:Kainic Acid / Q000009:adverse effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000473:pathology*; D012694:Serine / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D018690:Excitatory Amino Acid Agonists; D051025:bcl-Associated Death Protein; D012694:Serine; D051745:Protein Kinase C-delta; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase; D007608:Kainic Acid