| First Author | Cho KJ | Year | 2010 |
| Journal | Mol Cell Neurosci | Volume | 45 |
| Issue | 3 | Pages | 267-76 |
| PubMed ID | 20637286 | Mgi Jnum | J:171317 |
| Mgi Id | MGI:4949594 | Doi | 10.1016/j.mcn.2010.07.001 |
| Citation | Cho KJ, et al. (2010) Decisive role of apurinic/apyrimidinic endonuclease/Ref-1 in initiation of cell death. Mol Cell Neurosci 45(3):267-76 |
| abstractText | 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. |
