Nitric oxide-donor compounds inhibit lipoxygenase activity.
The nitric oxide (N0-releasing agents sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) inhibit dioxygenase activity of lipoxygenase in human platelets and human CHP100 neuroblastoma cells, leading the latter to necrosis. The effect of both NO-donors on the dioxygenase reaction was investigated by using soybean lipoxygenase type II (LOX-2) as a model for the mammalian enzyme. SNP and SNAP were competitive inhibitors of LOX-2, with inhibition constants of 525 microM and 710 microM, respectively. Both compounds inactivated LOX-2 by reducing the catalytic iron to the inactive Fe(II) form and counteracted the H2O2-mediated activation of the LOX-2 catalyzed dioxygenase reaction. Similarly, 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, by the inactivation of lipoxygenase, a key-enzyme for the arachidonic acid metabolism in human cells.
Maccarrone
M
M
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
Corasaniti
M T
MT
Guerrieri
P
P
Nisticò
G
G
Finazzi Agrò
A
A
D001792:Blood Platelets / Q000201:enzymology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D008084:Lipoxygenase / Q000097:blood / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009336:Necrosis; D009447:Neuroblastoma; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010105:Oxygenases / Q000037:antagonists & inhibitors* / Q000097:blood; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D014407:Tumor Cells, Cultured
D016859:Lipoxygenase Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010105:Oxygenases; D008084:Lipoxygenase; D010396:Penicillamine