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Apoptosis signal-regulating kinase 1 (Ask1) targeted small interfering RNA on ischemic neuronal cell death

 Hyun-Woo Kim  ;  Kyoung-Joo Cho  ;  Su Kyoung Lee  ;  Gyung W. Kim 
 BRAIN RESEARCH, Vol.1412 : 73-78, 2011 
Journal Title
Issue Date
Animals ; Brain/metabolism ; Brain/pathology* ; Brain Ischemia/genetics* ; Brain Ischemia/metabolism ; Brain Ischemia/pathology ; Cell Death ; MAP Kinase Kinase Kinase 5/genetics* ; MAP Kinase Kinase Kinase 5/metabolism ; Male ; Mice ; Neurons/metabolism ; Neurons/pathology* ; Phosphorylation ; RNA, Small Interfering ; Reperfusion ; Stroke/genetics* ; Stroke/metabolism ; Stroke/pathology
Stroke ; Cerebral infarction ; Apoptosis signal-regulating kinase 1 ; RNA interference ; Mice
Apoptosis signal-regulating kinase 1 (Ask1) is one of mitogen-activated protein kinase kinase kinase (MAPKKK) for cell differentiation and apoptosis. The aim of the present study is to evaluate whether RNA interference against Ask1 (Ask1-siRNA) down-regulates the expression of Ask1 and prevents apoptotic neuronal cell death after ischemia/reperfusion (I/R) in mice. Mice were subjected to intraluminal suture occlusion of the middle cerebral artery for 1h, followed by reperfusion. The Ask1-siRNA or a control-siRNA was introduced using osmotic pump intracerebroventricularly at 3days before I/R. The expression and mRNA of Ask1 were evaluated by Western blot and RT-PCR after I/R with time. Immunohistochemistry and TUNEL assay were also investigated to evaluate the effect of Ask1 on cerebral infarction by Ask1-siRNA treatment. The expression of Ask1 was increased significantly at 8h after I/R. The level of mRNA and protein of Ask1 down-regulated after treatment of Ask1-siRNA and subsequently cerebral infarction volume was reduced. Our results suggest the increased Ask1 expression induce apoptotic cell death after I/R. And we also demonstrated that Ask1-siRNA attenuates upregulation of Ask1, which was followed by the reduction of infarction in ischemic brain after I/R. Ask1-siRNA could represent a molecular target for prevention of ischemic stroke.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
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
Kim, Hyun Woo(김현우)
Lee, Su Kyoung(이수경)
Cho, Kyuong Joo(조경주)
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