Expression of death-associated protein kinase and recruitment to the tumor necrosis factor signaling pathway following brief seizures
Autor: | David C, Henshall, Tomohiro, Araki, Clara K, Schindler, Sachiko, Shinoda, Jing-Quan, Lan, Roger P, Simon |
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Rok vydání: | 2003 |
Předmět: |
Male
Tyrosine 3-Monooxygenase Fas-Associated Death Domain Protein Cell Count Hippocampus Receptors Tumor Necrosis Factor Rats Sprague-Dawley Antigens CD Seizures Animals Adaptor Proteins Signal Transducing Cerebral Cortex Kainic Acid Tumor Necrosis Factor-alpha Electroencephalography Amygdala Rats Enzyme Activation Death-Associated Protein Kinases Disease Models Animal 14-3-3 Proteins Receptors Tumor Necrosis Factor Type I Calcium-Calmodulin-Dependent Protein Kinases Apoptosis Regulatory Proteins Carrier Proteins Signal Transduction |
Zdroj: | Journal of neurochemistry. 86(5) |
ISSN: | 0022-3042 |
Popis: | 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. |
Databáze: | OpenAIRE |
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