J Korean Neurol Assoc.  2005 Aug;23(4):510-518.

Expression of Apurinic/apyrimidinic Endonuclease and Neuronal Apoptosis in the Striatum after Treatment of 3-Nitropropionic Acid in Mice

• Cho KJ
• Lee DJ
• Lee BI
• Kim GW

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.

Keyword

3-Nitropropionic acid; Apurinic/apyrimidinic endonuclese; Reactive oxygen species; Mananese tetrakis (40benzoic acid porphyrin); Reverse transcription polymerase chain reaction

MeSH Terms

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
DNA
RNA, Messenger
Reactive Oxygen Species
Succinate Dehydrogenase
Superoxides