title: Inhibitory effect of a synthetic protease inhibitor (gabexate mesilate) on the respiratory burst oxidase in human neutrophils.
abstract: We investigated the mechanism by which the synthetic protease inhibitor gabexate mesilate inhibits the production of the superoxide anion by human neutrophils. We found that gabexate mesilate suppressed SOD-inhibitable cytochrome c reduction in a dose-dependent manner in intact neutrophils activated with phorbol ester. Gabexate mesilate slightly scavenged the superoxide anion in the pyrogallol assay. The reagent also inhibited superoxide anion production in a dose-dependent manner in a cell-free oxidase-activating system. Translocation of the cytosolic respiratory burst oxidase components, the 47- and 65-kDa proteins, to membranes was suppressed by the reagent in intact cells stimulated with phorbol ester. Gabexate mesilate also reduced arachidonic acid-induced translocation of the components to the membrane fraction in the cell-free system. These results demonstrate that gabexate mesilate suppresses superoxide anion production by reducing the translocation of the 47- and 65-kDa proteins to the plasma membrane.
authors: Department of Surgery II, Osaka University Medical School.
authors: I
authors: I
authors: Ohashi
authors: J
authors: J
authors: Nishijima
authors: A
authors: A
authors: Murata
authors: H
authors: H
authors: Toda
authors: T
authors: T
authors: Kato
mesh_terms: D002462:Cell Membrane / Q000187:drug effects; D002474:Cell-Free System; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D016670:Gabexate / Q000494:pharmacology*; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000187:drug effects*; D019255:NADPH Oxidases; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects; D010084:Oxidation-Reduction; D012016:Reference Values; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D015842:Serine Proteinase Inhibitors; D013481:Superoxides; D016670:Gabexate; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C022709:superoxide-forming enzyme; D013755:Tetradecanoylphorbol Acetate