Expression of death-associated protein kinase and recruitment to the tumor necrosis factor signaling pathway following brief seizures.
Death-associated protein (DAP) kinase is calcium-regulated and known to function downstream of death receptors, prompting us to examine its role in the mechanism of seizure-induced neuronal death. Brief seizures were focally evoked in rats, eliciting neuronal death within the CA3 subfield of the hippocampus, and to a lesser extent, cortex. ... Western blotting confirmed expression of DAP kinase within hippocampus and cortex at the predicted weight of approximately 160 kDa. Immunohistochemistry revealed seizures triggered a significant increase in numbers of DAP kinase-expressing cells within CA3 and cortex, without affecting cell counts within seizure-resistant CA2 or the dentate gyrus. Numbers of DAP kinase-expressing cells were increased in relation to specific patterns of injury-causing seizure activity, electrographically defined. Seizures caused an early increase in DAP kinase binding to actin, and association with calmodulin. Co-immunoprecipitation studies also revealed seizures triggered binding of DAP kinase to the tumor necrosis factor receptor 1 and the Fas-associated death domain protein, commensurate with caspase-8 proteolysis. In contrast, within surviving fields of the hippocampus, DAP kinase interacted with the molecular chaperone 14-3-3. These data suggest DAP kinase is involved in the molecular pathways activated during seizure-induced neuronal death.
Mesh Terms:
14-3-3 Proteins, Adaptor Proteins, Signal Transducing, Amygdala, Animals, Antigens, CD, Apoptosis Regulatory Proteins, Calcium-Calmodulin-Dependent Protein Kinases, Carrier Proteins, Cell Count, Cerebral Cortex, Disease Models, Animal, Electroencephalography, Enzyme Activation, Fas-Associated Death Domain Protein, Hippocampus, Kainic Acid, Male, Rats, Rats, Sprague-Dawley, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Seizures, Signal Transduction, Tumor Necrosis Factor-alpha, Tyrosine 3-Monooxygenase
14-3-3 Proteins, Adaptor Proteins, Signal Transducing, Amygdala, Animals, Antigens, CD, Apoptosis Regulatory Proteins, Calcium-Calmodulin-Dependent Protein Kinases, Carrier Proteins, Cell Count, Cerebral Cortex, Disease Models, Animal, Electroencephalography, Enzyme Activation, Fas-Associated Death Domain Protein, Hippocampus, Kainic Acid, Male, Rats, Rats, Sprague-Dawley, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Seizures, Signal Transduction, Tumor Necrosis Factor-alpha, Tyrosine 3-Monooxygenase
J. Neurochem.
Date: Sep. 01, 2003
PubMed ID: 12911633
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