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KMID : 0877220040080020108
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Journal of Korean Epilepsy Society
2004 Volume.8 No. 2 p.108 ~ p.115
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Rapid Loss of Apurinic/Apyrimidinic Endonuclease and Subsequent Apoptosis in Kainate-Induced Seizure Model
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Shin Ha-Young
Lee Doo-Jae
Cho Kyoung-Joo
Kim Mi-Ae
Lee Yong-Hyun
Heo Kyoung
Kim Gyung-Whan
Lee Byung-In
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Abstract
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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.
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KEYWORD
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Kainate, Epilepsy·8-hydroxyguanine, APE, Apoptosis
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