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영구적 국소 대뇌 허혈 생쥐 모델에서 활성 산소종에 의한 세포고사 유도인자의 핵내 이동과 세포고사

Other Titles
 Nuclear Translocation of Apoptosis Inducing Factor and Subsequent DNA Fragmentation by Reactive Oxygen Species After Permanent Focal Cerebral Ischemia in Mice 
Authors
 조양제  ;  이용현  ;  조경주  ;  이두재  ;  김현우  ;  김현정  ;  이병인  ;  조상래  ;  김경환 
Citation
 Korean Journal of Stroke (대한뇌졸중학회지), Vol.7(2) : 214-223, 2005 
Journal Title
 Korean Journal of Stroke (대한뇌졸중학회지) 
ISSN
 1229-4101 
Issue Date
2005
Abstract
Background: Recently, the mitochondrial proapoptotic protein, apoptosis-inducing factor (AIF), and its nuclear translocation have been reported in caspase-independent neuronal apoptosis. However, it is not elucidated whether oxidative signaling is involved in the nuclear translocation of AIF and subsequent caspase-independent apoptotic cell death. We investigated whether oxidative signaling induces nuclear translocation of AIF and subsequent caspase- independent apoptosis-associated DNA fragmentation after permanent focal cerebral ischemia (FCI). Methods: Adult male ICR mice were subjected to permanent FCI by intraluminal suture blockade of middle cerebral artery. Immunohistochemistry and Western blot analysis were performed. Large-scale DNA fragmentation was evaluated by pulse field gel electrophoresis and apoptotic cell death was quantified. Manganese tetrakis (4-benzoic acid) porphyrin (MnTBAP), which mimics mitochondrial superoxide dismutase, was used to determinewhether the production of reactive oxygen species is required for the induction in AIF translocation. Results: Western blot analysis showed that the nuclear translocation of AIF occurred as early as 2 hours after permanent FCI. Immunostaining for AIF also confirmed early nuclear translocation of AIF after permanent FCI. Large-scale DNA fragmentation was detected 8 hours after permanent FCI. MnTBAP-treatment attenuated AIF translocation and blocked large-scale DNA fragmentation. Caspase-3 activity was similarly inhibited between the pan-caspase inhibitor- and MnTBAP-treated mice, but the amount of apoptosis-associated DNA fragmentation in the MnTBAP-treated mice was less than in the pan-caspase inhibitor-treated mice (P<0.001). In addition, infarction volume was also decreased by MnTBAP. Conclusions: These results suggest that reactive oxygen species induce the caspase-independent nuclear translocation of AIF and subsequent apoptosis-associated DNA fragmentation after permanent FCI.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Gyung Whan(김경환) ORCID logo https://orcid.org/0000-0001-7053-4372
Kim, Hyun Woo(김현우)
Lee, Byung In(이병인)
Cho, Sang Nae(조상래)
Cho, Yang Je(조양제)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/149941
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