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J Neurocrit Care 2008;1(2): 150-156.
일과성 국소 대뇌 허혈 생쥐 모델에서 APE/Ref-1 융합 아데노바이러스 처치에 의한 APE/Ref-1의 과발현 및 신경세포고사 감소
김현우, 조경주·이병인·김현정·김경환
연세대학교 의과대학 신경과학교실, 뇌졸중 및 신경-혈관집중치료실
Overexpressed Apurinic/Apyrimidinic Endonuclease/Redox Effector Factor-1 Using Adenoviral Vector Inhibits Induction of Neuronal Cell Death after Transient Ischemic Stroke in Mice
Hyun-Woo Kim, BS Kyoung-Joo Cho, MS, Byung-In Lee, MD, Hyun-Jeong Kim, MS and Gyung Whan Kim, MD, PhD
Stroke and Neurocritical Care Section, Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
ABSTRACT
Background: Despite the correlation between changes in the levels of apurinic/apyrimidinic endonuclease/redox effector factor-1 (APE/Ref-1), the DNA base excision repair protein, and ischemic neuronal damage, no studies have addressed the question of whether the overexpression or restoration of APE/Ref-1 may prevent ischemic neuronal cell death in vivo. Therefore, we investigated whether increasing APE/Ref-1 may inhibit the loss of APE/Ref-1 and DNA fragmentation, and prevent neuronal cell death after cerebral ischemia/reperfusion (I/R).
Methods: Adult male C57BL/6J mice were subjected to intraluminal suture occlusion of the middle cerebral artery for 1 hour followed by reperfusion. Pre-ischemic treatment of the adenoviral vector harboring an entire APE/Ref-1 gene sequence was introduced intrastriatally. Immunohistochemistry assays in AP sites, and TUNEL were performed.
Results: APE/Ref-1 was overexpressed by using adenoviral-vector-mediated APE/Ref-1 in striatum. Pre-ischemic administration of the Adenoviral vector harboring an APE/Ref-1 gene, by 4 or 24 hours after reperfusion, significantly decreased AP site and 8-OHdG, and subsequent inhibited the induction of apoptotic DNA fragmentation at 24 hours after I/R.
Conclusions: The overexpression of APE/Ref-1 can prevent induction of apoptotic cell death after I/R. Using adenoviral-vector-mediated APE/Ref-1 could represent a molecular target for prevention of ischemic neuronal cell death.
Key Words: Cerebral ischemia and/or reperfusion·DNA damage and repair·Stroke treatment·Adenoviral vectors
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