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

Authors
 Kyoung Joo Cho  ;  Hyun Jeong Kim  ;  Soo Chul Park  ;  Hyun Woo Kim  ;  Gyung Whan Kim 
Citation
 MOLECULAR AND CELLULAR NEUROSCIENCE, Vol.45(3) : 267-276, 2010 
Journal Title
 MOLECULAR AND CELLULAR NEUROSCIENCE 
ISSN
 1044-7431 
Issue Date
2010
MeSH
Adenoviridae/genetics ; Adenoviridae/metabolism ; Animals ; Cell Death/physiology* ; DNA Damage ; DNA Repair ; DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics ; DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism* ; Hippocampus/cytology ; Hippocampus/pathology ; Humans ; Kainic Acid/pharmacology ; Male ; Mice ; Neurons/drug effects ; Neurons/metabolism ; Neurons/pathology ; Peptides/genetics ; Peptides/metabolism ; RNA, Small Interfering/metabolism
Keywords
APE/Ref-1 ; Adenovirus ; siRNA ; APE small peptide ; TAT-mediated transduction ; Neutral antibody
Abstract
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S104474311000151X
DOI
10.1016/j.mcn.2010.07.001
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Gyung Whan(김경환) ORCID logo https://orcid.org/0000-0001-7053-4372
Kim, Hyun Woo(김현우)
Kim, Hyun Jeong(김현정)
Park, Soo Chul(박수철)
Cho, Kyuong Joo(조경주)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/101811
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