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

FEBS Letters

Oh, Esther¹  Tsuda, Masaaki¹  Tsuchiya, Tomofusa¹  Sano, Kuniaki¹  Tabuchi, Akiko¹ 

[1] Department of Microbiology, Faculty of Pharmaceutical Sciences, Okayama University, Tsushima-naka, Okayama 700, Japan

关键词: Nitric oxide (NO) AP-1;    Redox regulation;    S-nitrosylation;    Sodium nitroprusside (SNP);    Transcriptional factor;   

DOI  :  10.1016/0014-5793(94)00839-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown