Protein kinase Cdelta is associated with 14-3-3 phosphorylation in seizure-induced neuronal death.
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.
Kim
Yoon Sook
YS
Department of Anatomy and Neurobiology, School of Medicine, Institute of Health Science, Gyeongsang National University, Chilam-dong 92, Jinju, Gyeongnam 660-751, South Korea.
Choi
Mee Young
MY
Kim
Young Hee
YH
Jeon
Byeong Tak
BT
Lee
Dong Hoon
DH
Roh
Gu Seob
GS
Kang
Sang Soo
SS
Kim
Hyun Joon
HJ
Cho
Gyeong Jae
GJ
Choi
Wan Sung
WS
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
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