Production of C-type natriuretic peptide in human aortic endothelial cells induced by activation of protein kinase C

The effects of activators and inhibitors of protein kinase C (PKC) on the production of C-type natriuretic peptide (CNP) by cultured human aortic endothelial cells were examined. The PKC activators phorbol 12-myristate 13-acetate (PMA) and 1-oleoyl 2-acetyl glycerol (OAG) stimulated CNP release; the maximal effects were apparent at 4 h, at which time release was 934 and 205% of the control value, respectively. The PKC inhibitors staurosporine and H-7 did not affect basal CNP release, but each abolished the increase in CNP release induced by PMA or OAG. PKC was activated and translocated from cytosolic to membrane fractions in endothelial cells exposed to PMA or OAG; the maximal effect was apparent at 1 h. PMA and OAG each increased the abundance of CNP mRNA, with the maximal effect at 2 h. These data suggest that activation of PKC by PMA or OAG results in an increase in the abundance of CNP mRNA and subsequent enhancement of CNP production and release in human aortic endothelial cells.