SOD1 down-regulates NF-κB and c-Myc expression in mice after transient focal cerebral ischemia

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

Research output: Contribution to journalArticlepeer-review

98 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) are implicated in reperfusion injury after focal cerebral ischemia (FCI). Reactive oxygen species regulate activity of transcription factors like NF-κB. The authors investigated the role of ROS in NF-κB activity after FCI using transgenic mice that overexpressed human copper/zinc-superoxide dismutase (SOD1) and that had reduced infarction volume after FCI. Superoxide dismutase transgenic and wild-type mice were subjected to 1 hour of middle cerebral artery occlusion (MCAO) and subsequent reperfusion. Immunohistochemistry showed SOD1 overexpression attenuated ischemia-induced NF-κB p65 immunoreactivity. Colocalization of NF-κB and the neuronal marker, microtubule-associated proteins (MAPs), showed that NF-κB was up-regulated in neurons after FCI. Electrophoretic mobility shift assays showed that SOD1 overexpression reduced ischemia-induced NF-κB DNA binding activity. Supershift assays showed that DNA-protein complexes contained p65 and p50 subunits. Immunoreactivity of c-myc, an NF-κB downstream gene, was increased in the ischemic cortex and colocalized with NF-κB. Western blotting showed that SOD1 overexpression reduced NF-κB and c-Myc protein levels in the ischemic brain. Colocalization of c-Myc and TUNEL staining was observed 24 hours after FCI. The current findings provide the first evidence that SOD1 overexpression attenuates activation of NF-κB after transient FCI in mice and that preventing this early activation may block expression of downstream deleterious genes like c-myc, thereby reducing ischemic damage.

Original languageEnglish
Pages (from-to)163-173
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume21
Issue number2
DOIs
Publication statusPublished - 2001

Keywords

  • Apoptosis
  • Focal cerebral ischemia
  • Free radicals
  • NF-κB
  • Superoxide dismutase
  • c-Myc

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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