Kainate 유발 간질모델에서 Apurinic/Apyrimidinic Endonuclease의 빠른 소실과 이에 따른 세포고사
Rapid Loss of Apurinic/Apyrimidinic Endonuclease and Subsequent Apoptosis in Kainate-Induced Seizure Model
신하영, 이두재, 조경주, 김미애, 이용현, 허경, 김경환, 이병인,
소속 상세정보
신하영 ( Shin Ha-Young )
연세대학교 의과대학 신경과학교실
이두재 ( Lee Doo-Jae )
연세대학교 의과대학 신경과학교실
조경주 ( Cho Kyoung-Joo )
연세대학교 의과대학 신경과학교실
김미애 ( Kim Mi-Ae )
연세대학교 의과대학 신경과학교실
이용현 ( Lee Yong-Hyun )
연세대학교 의과대학 신경과학교실
허경 ( Heo Kyoung )
연세대학교 의과대학 신경과학교실
김경환 ( Kim Gyung-Whan )
연세대학교 의과대학 신경과학교실
이병인 ( Lee Byung-In )
연세대학교 의과대학 신경과학교실
KMID : 0877220040080020108
Abstract
Purpose: The DNA repair enzyme, apurinic/apyrimidinic endonuclease (APE) plays a role in base excision repair pathway involved in repairing apurinic/apyrimidinic (AP) site after oxidative stress. To reveal the relationship between APE and neuronal apoptosis associated with oxidative stress after kainate treatment, the temporal change of APE expression was investigated in kainate-induced seizure model.
Methods: Status epilepticus was induced by unilateral intrahippocampal injection of kainate. Superoxide anion radical production and DNA oxidation were evaluated by in situ detection of oxidized hydroethidine and 8-hydroxyguanine (8-OHG) immunoreactivity. APE expression was examined by Western blot and immunohistochemical analysis. DNA fragmentation was visualized with terminal deoxynucleotidyl transferase-mediated uridine 5´-triphosphate-biotin nick end labeling (TUNEL) staining.
Results: Cell loss occurred at 24 hr in CA1, CA2, and CA3 after kainate-injection. 8-OHG immunoreactivity and oxidized hydroethidine were increased comparing with control after kainate-injection. APE immunoreactivity was decreased 4 and 24 hours in the hippocampus after kainate-injection. TUNEL-positive cells were observed 24 hours but not 4 hours in hippocampus after kainate-injection. In double labeling with APE and TUNEL, TUNEL-positive cells did not show APE immunoreactivity. These data showed that cellular oxidative stress was increased, thereby APE was decreased in the hippocampus after kainate-injection. Also, it was shown that the reduction of APE preceded DNA fragmentation.
Conclusion: This study suggests that rapid loss of APE may produce the failure of DNA repair-machinary and then induce neuronal apoptosis following kainate-injection.
키워드
Kainate;Epilepsy·8-hydroxyguanine;APE;Apoptosis
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