Nitric oxide induces c-fos gene expression via cyclic AMP response element binding protein (CREB) phosphorylation in rat retinal pigment epithelium.

We have examined whether nitric oxide (NO) induces the expression of c-fos proto-oncogene and the phosphorylation of cyclic AMP response element binding protein (CREB) in the rat retina. NO donor sodium nitroprusside (SNP) was injected into the vitreal cavity of the eye, and the retina and retinal pigment epithelium (RPE) was analysed by in situ hybridization using single-stranded RNA probes for c-fos transcripts and by immunocytochemistry using an anti-phospho Ser-133 antibody 20 min after the injection of SNP, phosphorylated-CREB immunoreactivity was found in RPE cells and weakly in some cells of the INL. Forty-five min after the SNP injection, the expression of c-fos mRNA was detected in the RPE. These results suggested that NO induced the c-fos expression via the phosphorylation of CREB in RPE cells, as it has been demonstrated in PC12 cells that the transcription of c-fos gene was activated by the CREB phosphorylation.