DNA damage and repair system in spinal cord ischemia

Ruxian Lin, Glen Roseborough, Yafeng Dong, G. Melville Williams, Chiming Wei

Research output: Contribution to journalArticle

Abstract

Background and Purpose: Spinal cord ischemia-reperfusion injury may be initiated by a number of mediators, including reactive oxygen species. Recent studies have shown that human MutY homologue (hMYH), human 8-oxo-7,8-dihydrodeoxyguanine (8-oxoG) glycosylase (hOGG1), and human MutS homologue 2 (hMSH2) are important DNA mismatch repair genes. We hypothesized that ischemia-reperfusion injury in spinal cord causes DNA damage manifested by 8-oxoG production and activates the DNA repair system involving hMYH, hOGG1, and hMSH2. Methods: Spinal cords of rabbits were removed at 1, 3, 6, 24, and 48 hours after 30 minutes of infrarenal aortic occlusion. DNA damage was determined with 8-oxoG staining. The expression and localization of DNA repair enzymes, such as hMYH, hOGG1, and hMSH2, were studied with Western blot analysis and immunohistochemical staining. The level of apoptosis was determined with TUNEL study. Activation of caspase-3, an enzyme induced by cellular injury that leads to apoptosis by degrading cellular structural proteins, was also studied. Results: DNA damage monitored with 8-oxoG level was significantly present from 1 hour to 6 hours after reperfusion in gray matter neurons of ischemic spinal cord. The levels of hMYH, hOGG1, and hMSH2 were markedly increased in gray matter neurons at 6 hours after reperfusion. Caspase-3 was also induced at 6 hours to 24 hours after reperfusion in ischemic spinal cord. However, the peak level of TUNEL reactivity was found at 48 hours after reperfusion in spinal cord neurons. Conclusion: This study has shown, for the first time, the rapid expression of DNA damage-repair processes associated with spinal cord ischemia and subsequent reperfusion.

Original languageEnglish (US)
Pages (from-to)847-858
Number of pages12
JournalJournal of Vascular Surgery
Volume37
Issue number4
DOIs
Publication statusPublished - Apr 1 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Lin, R., Roseborough, G., Dong, Y., Melville Williams, G., & Wei, C. (2003). DNA damage and repair system in spinal cord ischemia. Journal of Vascular Surgery, 37(4), 847-858. https://doi.org/10.1067/mva.2003.150