0 556

Cited 28 times in

Knockdown of apoptosis signal-regulating kinase 1 affects ischaemia-induced astrocyte activation and glial scar formation.

Authors
 So Yeong Cheon  ;  Kyoung Joo Cho  ;  Juhyun Song  ;  Gyung Whan Kim 
Citation
 EUROPEAN JOURNAL OF NEUROSCIENCE, Vol.43(7) : 912-922, 2016 
Journal Title
EUROPEAN JOURNAL OF NEUROSCIENCE
ISSN
 0953-816X 
Issue Date
2016
MeSH
Animals ; Astrocytes/metabolism* ; Astrocytes/pathology ; Cell Line ; Cicatrix/metabolism* ; Glial Fibrillary Acidic Protein/genetics ; Glial Fibrillary Acidic Protein/metabolism ; Infarction, Middle Cerebral Artery/metabolism* ; Infarction, Middle Cerebral Artery/pathology ; MAP Kinase Kinase Kinase 5/genetics* ; MAP Kinase Kinase Kinase 5/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; p38 Mitogen-Activated Protein Kinases/metabolism
Keywords
apoptosis signal-regulating kinase 1 ; cerebral ischaemia ; glial scar formation ; reactive astrocyte ; small interfering RNA
Abstract
Reactive astrocytes play an essential role in determining the tissue response to ischaemia. Formation of a glial scar can block the neuronal outgrowth that is required for restoration of damaged tissue. Therefore, regulation of astrocyte activation is important; however, the mediator of this process has not been fully elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is an early responder to oxidative stress, and plays a pivotal role in the intracellular signalling pathway of apoptosis, inflammation, and differentiation. To confirm whether ASK1 mediates astrocyte activation and leads to glial scar formation after cerebral ischaemia, we conducted in vivo and in vitro experiments. C57BL/6 mice were subjected to occlusion of the middle cerebral artery, and astrocyte cultures were exposed to oxygen-glucose deprivation. After silencing of ASK1 , astrocyte-associated genes were downregulated, as seen with the use of microarrays. The glial fibrillary acidic protein (GFAP) level was decreased, and correlated with the reduction in the ASK1 level. In astrocytes, reduction in the ASK1 level decreased the activity of the p38 pathway, and the levels of transcription factors for GFAP and GFAP transcripts after hypoxia. In the chronic phase, ASK1 depletion reduced glial scar formation and conserved neuronal structure, which may lead to better functional recovery. These data suggest that ASK1 may be an important mediator of ischaemia-induced astrocyte activation and scar formation, and could provide a potential therapeutic target for treatment after ischaemic stroke.
Full Text
http://onlinelibrary.wiley.com/doi/10.1111/ejn.13175/abstract
DOI
10.1111/ejn.13175
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Gyung Whan(김경환) ORCID logo https://orcid.org/0000-0001-7053-4372
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146833
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links