Ohashi I, Nishijima J, Murata A, Toda H, Kato T
Department of Surgery II, Osaka University Medical School.
J Biochem. 1995 Nov;118(5):1001-6. doi: 10.1093/jb/118.5.1001.
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.
我们研究了合成蛋白酶抑制剂甲磺酸加贝酯抑制人中性粒细胞产生超氧阴离子的机制。我们发现，甲磺酸加贝酯在佛波酯激活的完整中性粒细胞中，以剂量依赖的方式抑制超氧化物歧化酶（SOD）可抑制的细胞色素c还原。在连苯三酚测定中，甲磺酸加贝酯可轻微清除超氧阴离子。该试剂在无细胞氧化酶激活系统中也以剂量依赖的方式抑制超氧阴离子的产生。在佛波酯刺激的完整细胞中，该试剂可抑制胞质呼吸爆发氧化酶成分（47 kDa和65 kDa蛋白）向细胞膜的转位。甲磺酸加贝酯还减少了无细胞系统中花生四烯酸诱导的这些成分向膜部分的转位。这些结果表明，甲磺酸加贝酯通过减少47 kDa和65 kDa蛋白向质膜的转位来抑制超氧阴离子的产生。
