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일과성 국소 대뇌 허혈 생쥐 모델에서 Apoptosis Signal-Regulating Kinase 1의 증가 및 Ask1 표적 siRNA 처치에 대한 대뇌 허혈 감소

Other Titles
 Increase of Apoptosis Signal-Regulating Kinase 1 and Inhibitory Effect of Ask1 Targeted Small Interfering RNA on Infarction after Ischemia/Reperfusion in Mice 
Authors
 김현우  ;  조경주  ;  김현정  ;  조양제  ;  이병인  ;  김경환 
Citation
 Journal of Neurocritical Care, Vol.1(2) : 143-149, 2008 
Journal Title
 Journal of Neurocritical Care 
ISSN
 2005-0348 
Issue Date
2008
Abstract
Background: Oxidative signal transduction has been crucial for the ischemic neuronal cell death. Apoptosis signal-regulating kinase 1 (Ask1), mitogen-activated protein MAP kinase kinase kinase 5, activated by oxidative stress which induces apoptotic signal pathway. We investigated the expression of Ask1 after ischemia/reperfusion. And siRNA targeting Ask1 could efficiently attenuate the cerebral infarction volume. Methods: Adult male ICR mice were subjected to middle cerebral artery occlusion (MCAO) for 60 minutes followed by reperfusion. The expression and mRNA of Ask1 were evaluated by Western blot, RT-PCR and immunohistochemistry at various time points after reperfusion. Ask1 and cell death were also investigated by Western blot analysis, immunohistochemistry and TUNEL assay to evaluate the effect of Ask1 on cerebral infarction by treatment with siRNA targeting Ask1. Results: The expression of Ask1 was increased as early as 1 hour after ischemia/reperfusion and continued to 24 hours in ischemic brain compared to nonischemic brain. Double immunofluorescent staining demonstrated that Ask1 expression was colocalized in DNA damaged cells after ischemia/reperfusion. After treatment of Ask1-siRNA, down-regulation was confirmed by that the level of mRNA and protein of Ask1 was decreased and subsequently led to reduce cerebral infarction volume. Conclusion: Our results suggest the increased Ask1 expression induce apoptotic DNA damage after ischemia/reperfusion. And also we demonstrated that Ask1-siRNA attenuates upregulation of Ask1, which was followed by the reduction of infarction volume in ischemic brain after ischemia/reperfusion. Ask1-siRNA could represent a molecular target for prevention of ischemic stroke
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Appears in Collections:
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)
Kim, Hyun Jeong(김현정)
Lee, Byung In(이병인)
Cho, Kyuong Joo(조경주)
Cho, Yang Je(조양제)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108373
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