• C He, A R Stroink, and C X Wang.
• School of Biological Sciences, Illinois State University, Normal, IL 61790, USA; Central Illinois Neuroscience Foundation, Bloomington, IL 61701, USA.
• Neuroscience. 2014 Jan 31;258:254-62.

AbstractDeath-associated protein kinase (DAPK) has been found promoting cell death under stress conditions, including cell death during brain ischemia. However, little is known about the mechanisms how DAPK is involved in the neuronal death-promoting process during ischemia. The present study was to examine the DAPK signal transduction pathways using an ischemia mimicking model, oxygen glucose deprivation (OGD). OGD was induced by incubating SH-SY5Y neuroblastoma cells in glucose-free culture medium flushed with a mixture of N₂ and CO₂. DAPK expression was inhibited by transfection of SH-SY5Y cells with DAPK short hairpin RNA (shRNA). Cell death induced by OGD exposure was assessed by Annexin V-FITC and propidium iodide (PI) assay. Protein expressions were examined by Western blot and protein interactions were detected with immunoprecipitation followed by Western blot. OGD treatment resulted in neuronal death and led to DAPK activation as demonstrated by increase of DAPK (active form) and decrease of phospho-DAPK (inactive form). The activation of DAPK in turn led to BimEL up-regulation and endoplasmic reticulum (ER) stress activation. Further analyses showed that DAPK mediated BimEL expression through extracellular signal-regulated protein kinase1/2 (ERK1/2) inactivation and c-Jun-N-terminal kinase1/2 (JNK1/2) activation. These findings revealed novel signal transduction pathways leading to neuronal death in response to OGD.Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

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