197 209

Cited 17 times in

Apoptosis signal-regulating kinase 1 (ASK1) is linked to neural stem cell differentiation after ischemic brain injury

Authors
 Juhyun Song  ;  Kyoung Joo Cho  ;  So Yeong Cheon  ;  Sa-Hyun Kim  ;  Kyung Ah Park  ;  Won Taek Lee  ;  Jong Eun Lee 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.45(12) : 69, 2013 
Journal Title
 EXPERIMENTAL AND MOLECULAR MEDICINE 
ISSN
 1226-3613 
Issue Date
2013
MeSH
Animals ; Cell Death ; Infarction, Middle Cerebral Artery/metabolism* ; Lipopolysaccharides/pharmacology ; MAP Kinase Kinase Kinase 5/genetics ; MAP Kinase Kinase Kinase 5/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; Neural Stem Cells/cytology ; Neural Stem Cells/drug effects ; Neural Stem Cells/metabolism* ; Neurogenesis* ; Neuropeptides/genetics ; Neuropeptides/metabolism ; p38 Mitogen-Activated Protein Kinases/genetics ; p38 Mitogen-Activated Protein Kinases/metabolism
Keywords
Animals ; Cell Death ; Infarction, Middle Cerebral Artery/metabolism* ; Lipopolysaccharides/pharmacology ; MAP Kinase Kinase Kinase 5/genetics ; MAP Kinase Kinase Kinase 5/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; Neural Stem Cells/cytology ; Neural Stem Cells/drug effects ; Neural Stem Cells/metabolism* ; Neurogenesis* ; Neuropeptides/genetics ; Neuropeptides/metabolism ; p38 Mitogen-Activated Protein Kinases/genetics ; p38 Mitogen-Activated Protein Kinases/metabolism
Abstract
Neural stem cells (NSCs) have been suggested as a groundbreaking solution for stroke patients because they have the potential for self-renewal and differentiation into neurons. The differentiation of NSCs into neurons is integral for increasing the therapeutic efficiency of NSCs during inflammation. Apoptosis signal-regulating kinase 1 (ASK1) is preferentially activated by oxidative stress and inflammation, which is the fundamental pathology of brain damage in stroke. ASK1 may be involved in the early inflammation response after stroke and may be related to the differentiation of NSCs because of the relationship between ASK1 and the p38 mitogen-activated protein kinase pathway. Therefore, we investigated whether ASK1 is linked to the differentiation of NSCs under the context of inflammation. On the basis of the results of a microarray analysis, we performed the following experiments: western blot analysis to confirm ASK1, DCX, MAP2, phospho-p38 expression; fluorescence-activated cell sorting assay to estimate cell death; and immunocytochemistry to visualize and confirm the differentiation of cells in brain tissue. Neurosphere size and cell survival were highly maintained in ASK1-suppressed, lipopolysaccharide (LPS)-treated brains compared with only LPS-treated brains. The number of positive cells for MAP2, a neuronal marker, was lower in the ASK1-suppressed group than in the control group. According to our microarray data, phospho-p38 expression was inversely linked to ASK1 suppression, and our immunohistochemistry data showed that slight upregulation of ASK1 by LPS promoted the differentiation of endogenous, neuronal stem cells into neurons, but highly increased ASK1 levels after cerebral ischemic damage led to high levels of cell death. We conclude that ASK1 is regulated in response to the early inflammation phase and regulates the differentiation of NSCs after inflammatory-inducing events, such as ischemic stroke.
Files in This Item:
T201304061.pdf Download
DOI
10.1038/emm.2013.134
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Park, Kyung Ah(박경아)
Song, Ju Hyun(송주현)
Lee, Won Taek(이원택) ORCID logo https://orcid.org/0000-0001-7348-9562
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
Cheon, So Yeong(전소영)
Cho, Kyuong Joo(조경주)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/88489
사서에게 알리기
  feedback

qrcode

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

Browse