Expression of Apurinic/apyrimidinic Endonuclease and Neuronal Apoptosis in the Striatum after Treatment of 3-Nitropropionic Acid in Mice.
- Author:
Kyuong Joo CHO
1
;
Doo Jae LEE
;
Byung In LEE
;
Gyung Whan KIM
Author Information
1. Department of Neurology, Institue of Brain Research, Yonsei University College of Medicine, Seoul, Korea. gyungkim@yumc.yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
3-Nitropropionic acid;
Apurinic/apyrimidinic endonuclese;
Reactive oxygen species;
Mananese tetrakis (40benzoic acid porphyrin);
Reverse transcription polymerase chain reaction
- MeSH:
Animals;
Apoptosis*;
Blotting, Western;
Cell Death;
DNA;
DNA Damage;
DNA Fragmentation;
DNA Repair;
Gene Expression;
Hominidae;
Humans;
Immunohistochemistry;
Mice*;
Mitochondria;
Neurodegenerative Diseases;
Neurons*;
Oxidative Stress;
Reactive Oxygen Species;
RNA, Messenger;
Stroke;
Succinate Dehydrogenase;
Superoxides
- From:Journal of the Korean Neurological Association
2005;23(4):510-518
- CountryRepublic of Korea
- Language:Korean
-
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.
