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Expression, interaction, and proteolysis of death‐associated protein kinase and p53 within vulnerable and resistant hippocampal subfields following seizures
Author(s) -
Araki Tomohiro,
Shinoda Sachiko,
Schindler Clara K.,
QuanLan Jing,
Meller Robert,
Taki Waro,
Simon Roger P.,
Henshall David C.
Publication year - 2004
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.10184
Subject(s) - hippocampal formation , hippocampus , programmed cell death , kainic acid , proteolysis , kinase , protein kinase a , neuroscience , ask1 , biology , microbiology and biotechnology , apoptosis , mitogen activated protein kinase kinase , biochemistry , receptor , enzyme , glutamate receptor
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 ∼160‐kD DAP kinase within injured ipsilateral hippocampus, commensurate with the appearance of an ∼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. © 2004 Wiley‐Liss, Inc.