Inhibition of endothelial nitric-oxide synthase by ceruloplasmin

The plasma copper protein ceruloplasmin (CP) was found to inhibit endotheli al nitric-oxide synthase activation in cultured endothelial cells, in line with previous evidence showing that the endothelium-dependent vasorelaxatio n of the aorta is impaired by physiological concentrations of ceruloplasmin . The data presented here indicate a direct relationship between the extent of inhibition of agonist-triggered endothelial nitric oxide synthase activ ation and CP-induced enrichment of the copper content of endothelial cells. Copper discharged by CP was mainly localized in the soluble fraction of ce lls. The subcellular distribution of the metal seems to be of relevance to the inhibitory effect of CP, because it was mimicked by copper chelates, li ke copper-histidine, able to selectively enrich the cytosolic fraction of c ells, but not by copper salts, which preferentially located the metal to th e particulate fraction.