NITRIC OXIDE-DONOR COMPOUNDS INHIBIT LIPOXYGENASE ACTIVITY

The nitric oxide (NO)-releasing agents sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) inhibit dioxygenase activity of lipoxygenase in human platelets and human CHP100 neuroblastoma cell, leading the latter to necrosis. The effect of both NO-donors on the di oxygenase reaction was investigated by using soybean lipoxygenase type II (LOX-2) as a model for the mammalian enzyme. SNP and SNAP were com petitive inhibitors of LOX-2, with inhibition constants of 525 mu M an d 710 mu M, respectively. Both compounds inactivated LOX-2 by reducing the catalytic iron to the inactive Fe(II) form and counteracted the H 2O2-mediated activation of the LOX-2-catalyzed dioxygenase reaction. S imilarly, the co-oxidative and per oxidative activities of LOX-2 were also inhibited by the NO-releasing agents. These findings suggest that the biological role played by NO can be mediated, at least in part, b y the inactivation of lipoxygenase, a key-enzyme for the arachidonic a cid metabolism in human cells. (C) 1996 Academic Press, Inc.