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Ichiro Ohashi, Junichi Nishijima, Atsuo Murata, Hitoshi Toda, Takeshi Kato, Hirohito Hayashida, Hitoshi Shiozaki, Morito Monden, Inhibitory Effect of a Synthetic Protease Inhibitor (Gabexate Mesilate on the Respiratory Burst Oxidase in Human Neutrophils, The Journal of Biochemistry, Volume 118, Issue 5, October 1995, Pages 1001–1006, https://doi.org/10.1093/jb/118.5.1001
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Abstract
We investigated the mechanism by which the synthetic proetease 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.