Superoxide during reperfusion contributes to caspase-8 expression and apoptosis after transient focal stroke

Yuiko Morita-Fujimura, Miki Fujimura, Takashi Yoshimoto, Pak H. Chan

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

Background and Purpose - Reactive oxygen species produced during reperfusion may play a detrimental role in focal cerebral ischemia (FCI). We examined the protein expression of caspase-8, which plays a major role in both Fas-dependent and cytochrome c-dependent apoptotic pathways after FCI with or without reperfusion. Caspase-8 expression after transient FCI was compared between wild-type and transgenic mice that overexpress the cytosolic antioxidant copper/zinc superoxide dismutase (SOD1). Methods - Adult male CD-1 mice were subjected to 1 hour of FCI and reperfusion or to permanent FCI by intraluminal blockade of the middle cerebral artery. DNA fragmentation was evaluated by genomic DNA gel electrophoresis. Caspase-8 expression was analyzed by Western blot. Results - Caspase-8 was significantly induced 4 hours after transient FCI and remained at an increased level until 24 hours, whereas it was not modified after permanent FCI. Genomic DNA gel electrophoresis showed DNA laddering in a pattern similar to that seen in apoptosis, with a small amount of background smear 24 hours after transient FCI, whereas 25 hours of permanent FCI resulted in less DNA laddering with a strong background smear. Caspase-8 induction was significantly reduced in SOD1 transgenic mice compared with wild-type mice 4 hours after transient FCI. Conclusions - The results suggest that increased reactive oxygen species production during reperfusion may contribute to the induction of caspase-8, thereby exacerbating apoptosis after FCI.

Original languageEnglish
Pages (from-to)2356-2361
Number of pages6
JournalStroke
Volume32
Issue number10
DOIs
Publication statusPublished - 2001

Keywords

  • Apoptosis
  • Cerebral ischemia, focal
  • DNA damage
  • Mice
  • Reperfusion injury
  • Superoxide dismutase

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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