Oxidative cellular damage and the reduction of APE/Ref-1 expression after experimental traumatic brain injury

A. Lewén, T. Sugawara, Y. Gasche, M. Fujimura, P. H. Chan

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

The DNA repair enzyme, apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1), is involved in base excision repair of apurinic/apyrimidinic sites after oxidative DNA damage. We investigated the expression of APE/Ref-1 and its relationship to oxidative stress after severe traumatic brain injury produced by controlled cortical impact in normal mice, and in mice over- or underexpressing copper-zinc superoxide dismutase (SOD1TG and SOD1KO, respectively). Oxygen free radical-mediated cellular injury was visualized with 8-hydroxyguanine immunoreactivity as a marker for DNA oxidation, and in situ hydroethidine oxidation as a marker for superoxide production. After trauma there was a reduced expression of APE/Ref-1 in the ipsilateral cortex and hippocampus that correlated with the gene dosage levels of cytosolic superoxide dismutase. The decrease in APE/Ref-1 expression preceded DNA fragmentation. There was also a close correlation between APE/Ref-1 protein levels 4 h after trauma and the volume of the lesion 1 week after injury. Our data have demonstrated that reduction of APE/Ref-1 protein levels correlates closely with the level of oxidative stress after traumatic brain injury. We suggest that APE/Ref-1 immunoreactivity is a sensitive marker for oxidative cellular injury.

Original languageEnglish
Pages (from-to)380-390
Number of pages11
JournalNeurobiology of Disease
Volume8
Issue number3
DOIs
Publication statusPublished - 2001 Jan 1

Keywords

  • Cellular injury
  • DNA fragmentation
  • DNA oxidation
  • DNA repair
  • Mice
  • Outcome
  • Oxidative stress
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neurology

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