Evidence that neuronal Notch-1 promotes JNK/c-Jun activation and cell death following ischemic stress

Cheng, Yi-Lin, Choi, Yuri, Seow, Wei Lun, Manzanero, Silvia, Sobey, Christopher G., Jo, Dong-Gyu and Arumugam, Thiruma V. (2014) Evidence that neuronal Notch-1 promotes JNK/c-Jun activation and cell death following ischemic stress. Brain Research, 1586 193-202. doi:10.1016/j.brainres.2014.08.054


Author Cheng, Yi-Lin
Choi, Yuri
Seow, Wei Lun
Manzanero, Silvia
Sobey, Christopher G.
Jo, Dong-Gyu
Arumugam, Thiruma V.
Title Evidence that neuronal Notch-1 promotes JNK/c-Jun activation and cell death following ischemic stress
Journal name Brain Research   Check publisher's open access policy
ISSN 0006-8993
1872-6240
Publication date 2014-10-24
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.brainres.2014.08.054
Volume 1586
Start page 193
End page 202
Total pages 10
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2015
Language eng
Subject 2800 Neuroscience
2728 Clinical Neurology
1309 Developmental Biology
1312 Molecular Biology
Abstract Notch signaling is a highly conserved pathway that regulates cell fate decisions during embryonic development. We have recently identified that in ischemic stroke, activity of γ-secretase and the resulting Notch activation may endanger neurons by modulating NF-κB and HIF-1α pathways. Notch signaling can also modulate MAPK-related pathways. However, the role of γ-secretase-mediated Notch signaling in activating MAPK following ischemic stroke has not been investigated. We used control and NICD1-overexpressing HEK and SH-SY5Y cell lines, and inhibitors of γ-secretase and JNK, to explore novel roles of Notch in modulating cell death following ischemic stress in vitro. Our findings indicate that expression of NICD1, JNK/cJun, p38-MAPK and the pro-apoptotic marker, cleaved caspase-3, increased during ischemic conditions. γ-Secretase inhibitors reduced ischemia-induced increase in NICD1 and JNK/p-cJun. Furthermore, NICD overexpression augmented JNK/cJun levels and cell death under these conditions. These results suggest that Notch signaling contributes to the pathogenesis of ischemic stroke, in part by promoting JNK/cJun signaling. These results provide further support for the potential use of γ-secretase inhibitors as therapy for ischemic stroke.
Keyword Notch
Ischemic stroke
γ-Secretase
MAPK
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Biomedical Sciences Publications
 
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