Decisive role of apurinic/apyrimidinic endonuclease/Ref-1 in initiation of cell death

作者：Cho Kyoung Joo; Kim Hyun Jeong; Park Soo Chul; Kim Hyun Woo; Kim Gyung Whan^*

来源：Molecular and Cellular Neuroscience, 2010, 45(3): 267-276.

DOI：10.1016/j.mcn.2010.07.001

• APE/Ref-1
• Adenovirus
• siRNA
• APE small peptide
• TAT-mediated transduction
• Neutral antibody

The apurinic/apyrimidinic endonuclease/redox effector factor-1 (APE/Ref-1) is involved in the base excision repair of apurinic/apyrimidinic sites induced by oxidative DNA damage. APE/Ref-1 was decreased by kainic acid (KA) injury in a time-dependent manner at the level of proteins, not transcripts. We investigated whether alteration of APE/Ref-1 amounts would influence hippocampal cell fate, survival or death, after KA injury. Overexpression of APE/Ref-1 using adenovirus and restoration of APE small peptides significantly reduced KA-induced hippocampal cell death. Both silencing of APE/Ref-1 by siRNA and inhibition of endonuclease by an antibody significantly increased caspase-3 activity and apoptotic cell death triggered from the early time after exposure to KA. These findings suggest that cell death is initiated by reducing APE/ Ref-1 protein and inhibiting its repair function in spite of enough protein amounts. In conclusion, APE/Ref-1 may be a regulator of cell death initiation, and APE small peptides could provide molecular mechanism-based therapies for neuroprotection in progressive excitotoxic neuronal damage.

• 出版日期2010-11