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국소 대뇌 허혈 및 재관류 후 생쥐 모델에서 활성 산소 제거제(MnTBAP)에 의한 Endonuclease G의 조기 핵 내 이동방지 및 뇌경색 감소

Other Titles
 Treatment with MnTBAP Protects Against Early Nuclear Translocation of Endonuclease G and Reduces Cerebral Infarction after Focal Cerebral Ischemia/Reperfusion in Mice 
Authors
 김현우  ;  조경주  ;  김경환  ;  이병인  ;  조양제  ;  김현정 
Citation
 Journal of the Korean Neurological Association, Vol.25(4) : 535-543, 2007 
Journal Title
 Journal of the Korean Neurological Association 
ISSN
 1225-7044 
Issue Date
2007
Keywords
Endonuclease G ; DNA fragmentation ; Transient focal cerebral ischemia ; MnTBAP
Abstract
Background: Reactive Oxygen Species (ROS) have been implicated in the pathophysiology of brain injury after ischemia/reperfusion. Recently, it has been reported that endonuclease G (EndoG), a mitochondrial protein, is activated by neuronal excitotoxicity and translocated into nucleus inducing apoptosis. However, it is not elucidated whether ROS are involved in the nuclear translocation of EndoG in focal cerebral ischemia/reperfusion in mice. We investigated whether treatment of manganese tetrakis (4-benzoic acid) porphyrin (MnTBAP) protects against early nuclear translocation of EndoG and reduces cerebral infarction after ischemia/reperfusion in mice. Methods: Adult male mice were subjected to middle cerebral artery occlusion (MCAO) for 60 min, followed by reperfusion. Immunohistochemistry and Western blot analysis for EndoG were performed at various time points after ischemia/reperfusion. Double staining with EndoG and Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labeling (TUNEL) was also performed. MnTBAP was used to determine whether the production of ROS could inhibit translocation of EndoG into the nucleus. Results: Western blot analysis and Immunohistochemistry of EndoG showed that nuclear EndoG was detected as early as 4 hrs after reperfusion, and mitochondrial EndoG was significantly reduced at the same time. Double staining with EndoG and TUNEL showed a spatial relationship between EndoG expression and DNA fragmentation. MnTBAP-treated mice showed that the translocation of EndoG was attenuated in comparison with the vehicle- treated mice and decreased infarction volume after ischemia/reperfusion. Conclusions: MnTBAP reduced the generation of ROS, and inhibited the early translocation of EndoG, which was followed by the reduction of infarction volume in the ischemic brain after ischemia/reperfusion.KeyWords:Endonuclease G, DNA fragmentation, Transient focal cerebral ischemia, MnTBAP
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Appears in Collections:
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
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 Jung(김현정)
Lee, Byung In(이병인)
Cho, Kyuong Joo(조경주)
Cho, Yang Je(조양제)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96609
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