The adenoviral vector-mediated increase in apurinic/apyrimidinic endonuclease inhibits the induction of neuronal cell death after transient ischemic stroke in mice.
Despite the correlation between changes in the levels of apurinic/apyrimidinic endonuclease and ischemic neuronal damage, no studies have addressed the question of whether increased APE/Ref-1 can prevent ischemic neuronal cell death in vivo. Using an adenoviral vector, we investigated whether increased APE/Ref-1 can inhibit the loss of APE/Ref-1 and thereby prevent oxidative DNA damage after transient focal cerebral ischemia. Mice were subjected to intraluminal suture occlusion of the middle cerebral artery for 1 h, followed by reperfusion. Pre-ischemic treatment of the adenoviral vector was introduced intracerebrally. An adenoviral vector harboring the entire APE/Ref-1 gene sequence or a control virus without the APE/Ref-1 sequence was introduced 3 days before ischemia/reperfusion (I/R). The reduction of APE/Ref-1 occurred before DNA fragmentation, which was shown by temporal and spatial analysis. Increased APE/Ref-1 significantly decreased DNA damage and infarct volume after I/R. In conclusion, increased APE/Ref-1 enhanced DNA repair and inhibited the induction of ischemic oxidative DNA damage and cerebral infarction after I/R.
Kim
Hyun-Woo
HW
Department of Neurology and Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University, Seoul, Republic of Korea.
Cho
Kyoung-Joo
KJ
Park
Soo-Chul
SC
Kim
Hyun-Jeong
HJ
Kim
Gyung W
GW
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000235:genetics; D002560:Cerebrovascular Circulation / Q000502:physiology; D053938:DNA Fragmentation; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005609:Free Radicals / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D015427:Reperfusion Injury / Q000209:etiology / Q000235:genetics* / Q000473:pathology
D005609:Free Radicals; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase