Modulation of AP-1 activity by nitric oxide (NO) in vitro: NO-mediated modulation of AP-1.
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 (NO2-). 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.
Tabuchi
A
A
Department of Microbiology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Sano
K
K
Oh
E
E
Tsuchiya
T
T
Tsuda
M
M
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004229:Dithiothreitol / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D016202:N-Methylaspartate / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000378:metabolism*
D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D009599:Nitroprusside; D009569:Nitric Oxide; D016202:N-Methylaspartate; D004229:Dithiothreitol