期刊
BRAIN RESEARCH
卷 1412, 期 -, 页码 73-78出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2011.07.018
关键词
Stroke; Cerebral infarction; Apoptosis signal-regulating kinase 1; RNA interference; Mice
资金
- Ministry of health & Welfare, Republic of Korea [A110023]
- National Research Foundation of Korea [NRF-20100012644]
- College of Medicine, Yonsei University [6-2010-0030]
- Korea Health Promotion Institute [A110023] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 1 h, followed by reperfusion. The Ask1-siRNA or a control-siRNA was introduced using osmotic pump intracerebroventricularly at 3 days 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 8 h 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. (C) 2011 Elsevier B.V. All rights reserved.
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