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[P1.32]: Death‐associated protein kinase activity is critical for glutamate‐induced apoptosis in cultured cortical neurons
Author(s) -
Yu X.Y.,
Ji Z.H.,
Sun L.,
Li W.J.
Publication year - 2008
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2008.09.082
Subject(s) - apoptosis , citation , glioblastoma , kinase , programmed cell death , library science , physics , chemistry , biology , computer science , cancer research , biochemistry
Death-associated protein kinase (DAPK) is a Ca/calmodulinregulated serine/threonine kinase that acts as a positive mediator of apoptosis in various death-signalling pathways. Increasing evidence indicate that the catalytic and expression of DAPK are also involved in neuronal death induced by cerebral ischemia and seizure. Previous works in our laboratory have shown that overexpression of DAPK is a component in glutamate-induced neuronal apoptosis cascade. Glutamate, the principal excitatory amino acid neurotransmitter in the central nervous system, is also a potential toxin leading to excitotoxicity that has been implicated in various neurological disorders ranging from acute insults such as stroke, hypoglycemia, trauma and epilepsy to chronic neurodegenerative states such as Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and Alzheimer’s disease. In this study, we investigated whether the DAPK activity plays a role in glutamate-induced apoptosis in cultured cortical neurons. Cultured neurons exhibited a prevailing form of apoptosis in a delayed time course after treatment of glutamate, and a significant increase ofDAPK expression in neuronswas found. A peptide,with a composition identical to the last 17 8C-terminal amino acids (SCNSGTSYNSISSVVSR) of DAPK that inhibiting the pro-apoptotic functions of DAPK, was synthesized and internalized into cultured neurons. Neurons treated with the peptide were resistant to the apoptotic effects induced by glutamate treatment. In contrast, a peptidewith the sameaminoacid composition, butwhose sequence was scrambled, did not block glutamate-induced apoptosis. These results suggest that DAPK plays an important role in glutamateinducedneuronal apoptosis, and that blockingDAPKactivitymaybe as a potential therapeutic target for excitotoxicity.