-
-
J Korean Neurol Assoc. 2005;23(4):510-518.
- 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
- 3-nitropropionic Acid 투여 후 마우스 선조체에서 Apurinic/Apyrimidinic Endonuclease의 발현과 신경세포고사
-
조경주, 이두재 이병인 김경환
-
연세대학교 의과대학 신경과학교실, 뇌연구소
- 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
Keywords :
- 초록
-
