Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) and DNA damage in the caudal region of acute and chronic spinal cord injured rats treated by embryonic neural stem cells.
The oxidative mechanisms of injury-induced damage of neurons within the spinal cord are not very well understood. We used a model of T8-T9 spinal cord injury (SCI) in the rat to induce neuronal degeneration. In this spinal cord injury model, unilateral avulsion of the spinal cord causes oxidative stress of neurons. We tested the hypothesis that apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1) regulates this neuronal oxidation mechanism in the spinal cord region caudal to the lesion, and that DNA damage is an early upstream signal. The embryonic neural stem cell therapy significantly decreased DNA-damage levels in both study groups - acutely (followed up to 7 days after SCI), and chronically (followed up to 28 days after SCI) injured animals. Meanwhile, mRNA levels of APE/Ref-1 significantly increased after embryonic neural stem cell therapy in acutely and chronically injured animals when compared to acute and chronic sham groups. Our data has demonstrated that an increase of APE/Ref-1 mRNA levels in the caudal region of spinal cord strongly correlated with DNA damage after traumatic spinal cord injury. We suggest that DNA damage can be observed both in lesional and caudal regions of the acutely and chronically injured groups, but DNA damage is reduced with embryonic neural stem cell therapy.
Dagci
T
T
Department of Physiology, School of Medicine, Bornova-Izmir, Turkey. taner.dagci@ege.edu.tr
Armagan
G
G
Konyalioglu
S
S
Yalcin
A
A
D000208:Acute Disease; D000818:Animals; D002420:Cauda Equina / Q000201:enzymology / Q000473:pathology / Q000601:surgery*; D002478:Cells, Cultured; D002908:Chronic Disease; D020552:Comet Assay; D004249:DNA Damage; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000201:enzymology / Q000473:pathology / Q000637:transplantation*; D005260:Female; D008124:Locomotion; D009410:Nerve Degeneration / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D009474:Neurons / Q000201:enzymology / Q000473:pathology / Q000637:transplantation*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D015854:Up-Regulation
D012333:RNA, Messenger; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase