J Korean Neurol Assoc > Volume 23(4); 2005 > Article
Journal of the Korean Neurological Association 2005;23(4): 510-518.
3-nitropropionic Acid 투여 후 마우스 선조체에서 Apurinic/Apyrimidinic Endonuclease의 발현과 신경세포고사
조경주, 이두재 이병인 김경환
연세대학교 의과대학 신경과학교실, 뇌연구소
Expression of Apurinic/apyrimidinic Endonuclease and Neuronal Apoptosis in the Striatum after Treatment of 3-Nitropropionic Acid in Mice
Kyuong Joo Cho
Department of Neurology, Institue of Brain Research, Yonsei University College of Medicine, Seoul, Korea
Abstract
Background: 3-Nitroporpionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase in mitochondria and can induce apoptosis-like cell death in the striatum. It has been reported that oxidative stress plays a role in the 3-NP induced neuronal damage. 3-NP induced striatal damage is implicated in the pathogenesis of several neurological diseases, such as chronic neurodegenerative diseases and stroke. The DNA repair enzyme, apurinic/apyrimidinic endonuclease (APE), is a multifunctional protein in the DNA base excision repair (BER) pathway. To clarify the relationship between APE and neuronal cell death associated with the apoptosis in the striatum was induced by 3-NP in vivo.
Methods: After intra-striatal injection of 3-NP, expression of the APE protein and mRNA were evaluated by Western blot, immunohistochemistry, RT-PCR and DNA fragmentation patterns. Oxidative DNA damage was investigated by detection of oxidized DNA, AP site and superoxide.
Results: Expression levels of APE was rapidly reduced as early as 1hr after injection of 3-NP. DNA fragmentation was observed 24 hours after 3-NP treatment but not 4 hours. APE gene expression was increased to 1hr after 3-NP treatment. The number of AP sites were reduced and the reduction of APE proteins were blocked by a superoxide scavenger, MnTBAP-treatment.
Conclusions: These results suggest that the reduction of APE is the preceding event of DNA fragmentation that causes apoptosis and a decrease of APE may be induced by ROS after 3-NP treatment. KeyWords:3-Nitropropionic acid, Apurinic/apyrimidinic endonuclese, Reactive oxygen species, Mananese tetrakis (40benzoic acid porphyrin), Reverse transcription polymerase chain reaction
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