Overexpression of copper-zinc superoxide dismutase attenuates acute activation of activator protein-1 after transient focal cerebral ischemia in mice

C. Y. Huang, M. Fujimura, Y. Y. Chang, P. H. Chan

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background and Purpose - Reactive oxygen species (ROS) have been implicated in reperfusion injury after focal cerebral ischemia (FCI). ROS are known to regulate the activity of transcription factors such as activator protein-1 (AP-1), which is a dimer consisting of members of the Jun and Fos families. We investigated the role of ROS in AP-1 activity after FCI using transgenic mice that overexpressed copper-zinc superoxide dismutase (SOD1) and that had reduced infarction volume after FCI. Methods - The SOD1 transgenic mice and their wild-type littermates were subjected to middle cerebral artery occlusion and reperfusion by intraluminal suture blockade. After 60 minutes of middle cerebral artery occlusion, mice were allowed to recover for 1, 2, and 4 hours before euthanasia. Protein expression of c-Jun and c-Fos was examined by immunohistochemistry and Western blotting. AP-1 DNA-protein binding activity was assessed by electrophoretic mobility shift assays. Results - In wild-type mice, immunohistochemistry demonstrated acute c-Jun and c-Fos activation in ischemic cortex and its outer boundary. Expression of both was reduced in SOD1 transgenic mice. Western blotting confirmed that SOD1 overexpression was associated with reduced c-Jun and c-Fos protein levels in ischemic brain. Electrophoretic mobility shift assays revealed that the ischemia-enhanced DNA binding activity observed in wild-type mice was reduced in SOD1 transgenic mice. Supershift assays indicated that c-Jun participated in the bound AP-1 complex. Conclusions - SOD1 overexpression prevents early activation of AP-1 after transient FCI in mice. This may block the expression of downstream target genes that are injurious, thereby reducing the infarction volume after transient FCI in mice.

Original languageEnglish
Pages (from-to)[d]741-747
JournalStroke
Volume32
Issue number3
DOIs
Publication statusPublished - 2001 Jan 1

Keywords

  • Cerebral ischemia, focal
  • Free radicals
  • Mice
  • Superoxide dismutase
  • Transcription factor AP-1
  • Transcription factors

ASJC Scopus subject areas

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

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