Bim and Noxa are candidates to mediate the deleterious effect of the NF-κB subunit RelA in cerebral ischemia

Ioana Inta, Stephan Paxian, Ira Maegele, Wen Zhang, Marina Pizzi, PierFranco Spano, Ilenia Sarnico, Sajjad Muhammad, Oliver Herrmann, Dragos Inta, Bernd Baumann, Hsiou Chi Liou, Roland M. Schmid, Markus Schwaninger

Research output: Contribution to journalArticlepeer-review

Abstract

The transcription factor nuclear factor κB (NF-κB) is well known for its antiapoptotic action. However, in some disorders, such as cerebral ischemia, a proapoptotic function of NF-κB has been demonstrated. To analyze which subunit of NF-κB is functional in cerebral ischemia, we induced focal cerebral ischemia in mice with a germline deletion of the p52 or c-Rel gene or with a conditional deletion of RelA in the brain. Only RelA deficiency reduced infarct size. Interestingly, expression of the proapoptotic BH3 (Bcl-2 homology domain 3)-only genes Bim and Noxa in cerebral ischemia depended on RelA and the upstream kinase IKK (IκB kinase). RelA stimulated Bim and Noxa gene transcription in primary cortical neurons and bound to the promoter of both genes. Thus, the deleterious function in cerebral ischemia is specific for the NF-κB subunit RelA and may be mediated through Bim and Noxa.

Original languageEnglish
Pages (from-to)12896-12903
Number of pages8
JournalJournal of Neuroscience
Volume26
Issue number50
DOIs
Publication statusPublished - Dec 13 2006

Keywords

  • Bim
  • c-Rel
  • Cerebral ischemia
  • Noxa
  • p52
  • RelA

ASJC Scopus subject areas

  • Neuroscience(all)

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