Rapid attenuation of AP-1 transcriptional factors associated with nitric oxide (NO)-mediated neuronal cell death

Akiko Tabuchi, Esther Oh, Akiko Taoka, Hiroaki Sakurai, Tomofusa Tsuchiya, Masaaki Tsuda

Research output: Contribution to journalArticlepeer-review


Stimulation of glutamate receptors causes several intracellular reactions including activation of activator protein-1 (AP-1) production and nitric oxide (NO) generation. Exposing mouse cerebellar granule cells to N- methyl-D-aspartate or kainate (KA) in culture induced an increase of AP-1 DNA binding activity that was blocked by further addition of sodium nitroprusside (SNP), a typical NO donor. Immunoblotting using anti-c-Fos antiserum revealed the specific attenuation of AP-1, although total protein synthesis was not affected. Since the level of c-fos mRNA expression stimulated by KA remained constant even after exposure to SNP, the AP-1 attenuation can be post- transcriptionally induced. SNP did not affect the Ca2+ influx into the cells stimulated by KA. The involvement of NO in the AP-1 attenuation was supported by the fact that potassium ferrocyanide (K4Fe(CN)6), an analogue of SNP but devoid of NO, failed to inhibit the AP-1 DNA binding activity stimulated by KA. SNP alone induced neuronal cell death, which was blocked by the simultaneous addition of antioxidants, superoxide dismutase and catalase, and an NO scavenger, suggesting a direct role of peroxynitrite in the cell death. In good agreement with these effects, the AP-1 attenuation by SNP was also blocked by antioxidants. These results indicated that post- transcriptional attenuation of AP-1 is involved in the early processes of NO- mediated neuronal cell death.

Original languageEnglish (US)
Pages (from-to)31061-31067
Number of pages7
JournalJournal of Biological Chemistry
Issue number49
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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