Early decrease in apurinic/apyrimidinic endonuclease is followed by DNA fragmentation after cold injury-induced brain trauma in mice

Yuiko Fujimura, Miki Fujimura, M. Kawase, P. H. Chan

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Apurinic/apyrimidinic endonuclease, a multifunctional protein in the DNA base excision repair pathway, plays a central role in repairing DNA damage caused by reactive oxygen species. We examined protein expression of apurinic/apyrimidinic endonuclease before and after cold injury-induced brain trauma in mice, where we have previously shown reactive oxygen species to participate. Immunohistochemistry showed the nuclear expression of apurinic/apyrimidinic endonuclease in the entire region of control brains. One hour after cold injury-induced brain trauma, nuclear immunoreactivity was predominantly decreased in the inner boundary of the lesion, whereas there was a slight increase in the outer boundary area. Four hours after cold injury-induced brain trauma, nuclear immunoreactivity was almost absent in the entire lesion, and remained so until 24h. At this time, a marked increase in apurinic/apyrimidinic endonuclease immunoreactivity was seen in the outer boundary zone. Western blot analysis of the sample from the non-ischemic area showed a characteristic 37,000 mol. wt band, which decreased markedly 24h after cold injury-induced brain trauma. A time-dependent increase in DNA fragmentation was also observed after cold injury-induced brain trauma.Our data provide the first evidence that apurinic/apyrimidinic endonuclease decreased rapidly in the lesion after cold injury-induced brain trauma, whereas it was significantly increased at the outer boundary zone. Although further examination is necessary to elucidate the direct relationship between apurinic/apyrimidinic endonuclease alteration and the pathogenesis of cold injury-induced brain trauma, our results suggest the possibility that an early decrease in apurinic/apyrimidinic endonuclease and failure of the DNA repair mechanism may contribute to DNA-damaged neuronal cell death after cold injury-induced brain trauma. Copyright (C) 1999 IBRO.

Original languageEnglish
Pages (from-to)1465-1473
Number of pages9
JournalNeuroscience
Volume93
Issue number4
DOIs
Publication statusPublished - 1999 Aug 1

Keywords

  • APE/Ref-1
  • Apoptosis
  • Cryogenic brain trauma
  • DNA base excision repair

ASJC Scopus subject areas

  • Neuroscience(all)

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