TY - JOUR
T1 - Nitric oxide-donor compounds inhibit lipoxygenase activity
AU - Maccarrone, Mauro
AU - Corasaniti, M. Tiziana
AU - Guerrieri, Pietro
AU - Nisticò, Giuseppe
AU - Agrò, Alessandro Finazzi
PY - 1996/2/6
Y1 - 1996/2/6
N2 - 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 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 μM and 710 μM, 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 peroxidative 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 lipoxygennse, a key-enzyme for the arachidonic acid metabolism in human cells.
AB - 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 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 μM and 710 μM, 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 peroxidative 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 lipoxygennse, a key-enzyme for the arachidonic acid metabolism in human cells.
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U2 - 10.1006/bbrc.1996.0193
DO - 10.1006/bbrc.1996.0193
M3 - Article
C2 - 8619794
AN - SCOPUS:0030048708
VL - 219
SP - 128
EP - 133
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -