Post-ischemic administration of peptide with apurinic/apyrimidinic endonuclease activity inhibits induction of cell death after focal cerebral ischemia/reperfusion in mice.
Previous scientific research has elucidated the correlation between changes in levels of the DNA base excision repair protein, apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1), and ischemic neuronal DNA damage. However, to date, no studies have addressed the question of whether treatment involving this protein's repair function may prevent ischemic neuron death in vivo. Therefore, we aimed to investigate whether treatment with APE peptide is sufficient to prevent neuron death after ischemia/reperfusion (I/R) in mice. Mice were subjected to intraluminal suture occlusion of the middle cerebral artery for 1h followed by reperfusion. Post-ischemic treatment with the peptide containing only the APE repair functional domain was introduced intracerebroventricularly. Endonuclease activity assay and immunohistochemistry were performed. Assays of apurinic/apyrimidinic (AP) sites, single-strand DNA breaks, caspase-3 activity, and cell death were examined and quantified. We found that post-ischemic administration of the APE peptide up to 4h after reperfusion significantly inhibited the induction of cell death and subsequent infarct volume, measured 24h 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. gyungkim@yuhs.ac
Cho
Kyoung-Joo
KJ
Lee
Byung I
BI
Kim
Hyun-Jeong
HJ
Kim
Gyung W
GW
D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D053904:DNA Breaks, Single-Stranded; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D013778:Tetrazolium Salts; D013997:Time Factors
D010455:Peptides; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; D004706:Endodeoxyribonucleases; D004722:Endoribonucleases; C021835:Serratia marcescens nuclease; D053148:Caspase 3; C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase