NITRIC-OXIDE AND CGMP ANALOGS ACTIVATE TRANSCRIPTION FROM AP-1-RESPONSIVE PROMOTERS IN MAMMALIAN-CELLS

Nitric oxide (NO) increases cytosolic guanylate cyclase activity and t hereby activates the cGMP signal transduction pathway, The cAMP and Ca 2+-phospholipid signal transduction pathways activate transcription fa ctors that bind to the cAMP response element (CRE) and phorbol ester r esponse element (TRE), respectively, Little is known about transcripti onal regulation of gene expression by NO/cGMP, In transient and stable transfection experiments and in microinjection studies we found that three different NO-releasing agents and two membrane-permeable cGMP an alogs activated TRE-regulated but not CRE-regulated reporter genes in rodent fibroblast and epithelial cell lines, Activation of TRE regulat ed genes by NO-releasing agents and cGMP analogs appeared to be mediat ed by the AP-1 (Jun/Fos) transcription factor complex because we obser ved increased DNA binding of AP-1 and increased junB and c-fos mRNA in cells treated with these agents, The mechanism of gene activation by NO/cGMP was distinct from that used by phorbol esters and cAMP because it was not associated with c-jun mRNA induction and was not observed with CRE-containing promoters.