Expression, interaction, and proteolysis of death-associated protein kinase and p53 within vulnerable and resistant hippocampal subfields following seizures.
Death-associated protein (DAP) kinase is a novel regulator of cell death whose in vivo target(s) and role in neuronal cell death remain uncertain. Since DAP kinase has been implicated in p53-mediated apoptosis, a pathway activated following epileptic brain injury, we examined the relationship between DAP kinase and p53 following seizures. Rats underwent brief (40-min) seizures evoked by intraamygdala kainic acid, which caused the death of ipsilateral CA3 neurons while preserving the contralateral CA3 subfield. Seizures caused a small decline in levels of the approximately 160-kD DAP kinase within injured ipsilateral hippocampus, commensurate with the appearance of an approximately 60-kD fragment, and proteolysis of the p53 inhibitor, murine double minute gene 2 (MDM2). Expression of p53 increased within the ipsilateral hippocampus, and DAP kinase was detected within p53 immunoprecipitates. In contrast, DAP kinase and MDM2 were not proteolyzed within the seizure damage-resistant contralateral hippocampus. Furthermore, DAP kinase and p53 did not interact within the contralateral hippocampus, and p53 cellular localization redistributed from the nucleus to cytoplasm commensurate with p53 proteolysis. These data suggest that DAP kinase may be involved in the p53 pathway during seizure-induced neuronal death.
Araki
Tomohiro
T
Robert S. Dow Neurobiology Laboratories, Legacy Research, 1225 NE 2nd Avenue, Portland, OR 97232, USA.
Shinoda
Sachiko
S
Schindler
Clara K
CK
Quan-Lan
Jing
J
Meller
Robert
R
Taki
Waro
W
Simon
Roger P
RP
Henshall
David C
DC
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002467:Cell Nucleus / Q000201:enzymology; D064550:Death-Associated Protein Kinases; D003714:Denervation; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D007113:Immunity, Innate / Q000502:physiology; D007608:Kainic Acid; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497208:Mdm2 protein, rat; D051736:Proto-Oncogene Proteins c-mdm2; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D007608:Kainic Acid