FEBS Letters · 1993 · 71 citations · 17 references
Life SciencesBiochemistryPharmacologyCell SignalingInflammationInnate ImmunityAntioxidant DefenseNadph MetabolismOxidative Damage To BiomoleculesOxidative Stress In InflammationReactive Oxygen SpeciesRedox SignalingCompetitive InhibitionIntraperitoneal AdministrationNadph Oxidase ActivityNadph Oxidase SignalingNadph OxidasesNicotinamide Adenine Dinucleotide Phosphate Oxidase ActivationPeritoneal MacrophagesSodium Dodecyl Sulfate-polyacrylamide Gel Electrophoresis
The effect of the oxidized form of neopterin (NP) on the NADPH-dependent superoxide-generating oxidase (NADPH-oxidase) was investigated in both whole-cell and cell-free activation systems by using peritoneal macrophages of rats which had received an intraperitoneal injection of mineral oil. In the whole-cell system, NP remarkably inhibited the generation of superoxides in macrophages stimulated with phorbol myristate acetate (PMA). NP also showed an significant suppression of the activation of superoxide-generating NADPH-oxidase in the cell-free system using solubilized membranes and sodium dodecyl sulfate (SDS) as a stimulant. The 50%-inhibitory concentration (IC50) of NP was about 1 microM in both assay systems. In a kinetic study, competitive inhibition of the NADPH-oxidase by NP was observed in the cell-free system with a calculated inhibition constant (Ki) of 6.50 microM. These findings suggest that NP may play an important role in the suppression of superoxide generation via the inhibition of the NADPH-oxidase in phagocytes.
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