Modulation of AP-1 activity by nitric oxide (NO) in vitro: NO-mediated modulation of AP-1

Akiko Tabuchi, Kuniaki Sano, Esther Oh, Tomofusa Tsuchiya, Masaaki Tsuda

Research output: Contribution to journalArticlepeer-review

98 Citations (Scopus)

Abstract

To understand the role of nitric oxide (NO) in controlling the specific DNA-binding activities of transcriptional factors, we investigated the in vitro effect of the NO-donor sodium nitroprusside (SNP) on the AP-1 activity of cultured mouse cerebellar granule cells. A gel-mobility assay showed that SNP inhibited AP-1 activity in the presence, but not the absence of dithiothreitol (DTT). This DTT-dependent inhibition of AP-1 activity by SNP corresponded with the activation of the chemical reactivity of SNP with DTT, which can be monitored by the production of nitrite (NO-2). In contrast, diamide, a typical sulfhydryl oxidizing agent, inhibited AP-1 activity in the absence of DTT and its inhibitory effect was reversed competitively by DTT. Studies using structurally or functionally related analogues of SNP demonstrated that S-nitrosylation of the AP-1 moiety mediated by some NO-carriers but not by free NO, which can be produced by the chemical reaction of SNP with DTT, was responsible for the inhibition of AP-1 activity, suggesting NO-mediated regulation of the AP-1 transcriptional factor.

Original languageEnglish
Pages (from-to)123-127
Number of pages5
JournalFEBS Letters
Volume351
Issue number1
DOIs
Publication statusPublished - Aug 29 1994

Keywords

  • Nitric oxide (NO) AP-1
  • Redox regulation
  • S-nitrosylation
  • Sodium nitroprusside (SNP)
  • Transcriptional factor

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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