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Regulation of DAPK activity attenuates neuronal cell death in transient focal cerebral ischemic rats
Author(s) -
Won Jinyoung,
Hong Yonggeun
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb619
Subject(s) - programmed cell death , medicine , ischemia , apoptosis , downregulation and upregulation , glutamate receptor , neuroprotection , cell , pharmacology , neuroscience , chemistry , biology , receptor , biochemistry , gene
Background Death‐associated protein kinase (DAPK), a positive mediator of many forms of cell death, is activated by glutamate excitotoxic signaling pathways after events such as cerebral ischemia. Purpose: We herein explored whether DAPK was an essential component of programmed neuronal cell death, by downregulating the activity thereof using an oxazolone‐based DAPK inhibitor. Results: In a focal cerebral ischemic (MCAO) model, rats exhibited brain injury accompanied by morphological changes, and altered molecular expression patterns, indicative of neuronal cell death. However, during DAPK inhibition, morphological differences in the dendrites of pyramidal neurons, and differences in programmed cell death, were observed compared to MCAO vehicle‐only rats. Significant decreases in Bax, caspase‐6, and LC3 expression levels were observed. In addition, a significant increase in Bcl2 expression was observed in the DAPK‐downregulated group compared to MCAO vehicle‐only rats, whereas the ischemic injury brain volume was reduced in MCAO rats treated with DAPK inhibitor vs. vehicle (P < 0.05). Suggestion: These data indicate that DAPK inhibition confers protection against neuronal cell death and cerebral ischemic injury. Accordingly, DAPK downregulation exhibits a therapeutic potential in treatment of transient focal ischemia and neurodegenerative diseases. Funding: 2012R1A1A2005089, 2013R1A2A2A01067169, KGM4611512