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Endothelial cell oxidant production: effect of NADPH oxidase inhibitors.

机译:内皮细胞氧化剂的产生:NADPH氧化酶抑制剂的作用。

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The effects of known leukocyte NADPH oxidase inhibitors on general cellular oxidant production in cultured human endothelial cells (EC) has been investigated. EC were stimulated with 10 nM phorbol 12-myristate 13-acetate and cellular oxidant production measured in the presence and absence of inhibitors that act on various substituents of the oxidase complex and its activation pathways. The effects of the cytosolic oxidase subunit translocation inhibitors, catechols (3,4-dihydroxybenzaldehyde, caffeic acid, and protocatechuic acid), ortho-methoxy-substituted catechols (apocynin, vanillin, and 4-nitroguaiacol), and quinone, 1,4-naphthoquinone; flavoprotein inhibitors, diphenylene iodonium and quinacrine; haem ligands, imidazole and pyridine; directly acting thiol reagents, disulfiram and penicillamine; NADPH analogue, Cibacron Blue; redox active inhibitors, quercetin and esculetin; intracellular calcium antagonist, TMB-8; and calmodulin antagonists, W-7 and trifluoperazine, were determined. All compounds reduced oxidant production in stimulated EC. These findings add to previous observations suggesting the presence of a functionally active NADPH oxidase in EC. Identifying the major cellular reactive oxygen species source in perturbed EC will provide new insights into our understanding of endothelial dysfunction, which has been hypothesized to be a major contributing factor in the pathogenesis of atherosclerosis.
机译:已经研究了已知的白细胞NADPH氧化酶抑制剂对培养的人内皮细胞(EC)中一般细胞氧化剂产生的影响。用10 nM佛波醇12-肉豆蔻酸酯13-乙酸酯刺激EC,并在存在和不存在作用于氧化酶复合物各种取代基及其激活途径的抑制剂的条件下测量细胞氧化剂的产生。胞质氧化酶亚基易位抑制剂,儿茶酚(3,4-二羟基苯甲醛,咖啡酸和原儿茶酸),邻甲氧基取代的儿茶酚(阿波西宁,香兰素和4-硝基愈创木酚)和醌的作用:1,4-萘醌黄素蛋白抑制剂,二亚苯基碘鎓和奎纳克林;血红素配体,咪唑和吡啶;直接作用的硫醇试剂,双硫仑和青霉胺; NADPH类似物,烟酸蓝;氧化还原活性抑制剂槲皮素和七叶皂甙;细胞内钙拮抗剂TMB-8;测定钙调蛋白拮抗剂W-7和三氟拉嗪。所有化合物均可降低刺激性EC中的氧化剂产生。这些发现增加了以前的观察结果,提示在EC中存在功能活跃的NADPH氧化酶。在扰动的EC中识别主要的细胞活性氧物种来源将为我们对内皮功能障碍的理解提供新的见解,据认为这是动脉粥样硬化发病机理的主要促成因素。

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