STUDIES ON THE ANTI-INFLAMMATORY ACTIVITY OF EBSELEN - EBSELEN INTERFERES WITH GRANULOCYTE OXIDATIVE BURST BY DUAL INHIBITION OF NADPH OXIDASE AND PROTEIN KINASE-C
STUDIES ON THE ANTI-INFLAMMATORY ACTIVITY OF EBSELEN - EBSELEN INTERFERES WITH GRANULOCYTE OXIDATIVE BURST BY DUAL INHIBITION OF NADPH OXIDASE AND PROTEIN KINASE-C
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DOI：
10.1016/0006-2952(89)90211-6
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发表时间：
1989-02-15
影响因子：
5.8
通讯作者：
MOLDEUS, P
中科院分区：
文献类型：
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作者：
COTGREAVE, IA;DUDDY, SK;MOLDEUS, P
Ebselen（PZ 51，2-苯基-1，2-苯并异硒唑-3-（2 H）-酮）被证明是由佛波醇肉豆蔻酸酯乙酸酯刺激的人粒细胞氧化爆发的抑制剂（IC 50 25 μ M）。估计的初级氧代谢物的爆发是复杂的氧化还原化学的Ebselen。依布硒啉通过部分纯化的NADPH氧化酶制剂抑制NADPH刺激的超氧化物生成，IC 50为0.5-1.0 μ M。依布硒啉还显示出抑制部分纯化的Ca 2+和磷脂依赖性蛋白激酶C的活性（IC 50约为100%）。0.5μ M）。在完整细胞中，佛波酯刺激的蛋白质磷酸化被Ebselen抑制（IC 50 ca. 50 μ M）。依布硒啉的这些药效学特性在其体内抗炎活性方面进行了讨论。研究结果还讨论了Ebselen与细胞巯基组分相互作用的已知能力，特别是研究的酶的关键巯基组分。
Ebselen (PZ51, 2-phenyl-1,2-benzoisoselenazol-3-(2H)-one) was shown to be an inhibitor of human granulocyte oxidative burst stimulated by phorbol myristate acetate (IC50 25 .mu.M). Estimation of the primary oxygen metabolites of the burst was complicated by the redox chemistry of Ebselen. Ebselen inhibited NADPH-stimulated superoxide generation by a partially purified NADPH oxidase preparation with an IC50 of 0.5-1.0 .mu.M. Ebselen was also shown to inhibit the activity of partially purified Ca2+- and phospholipid-dependent protein kinase C (IC50 ca. 0.5 .mu.M). Phorbol ester-stimulated phosphorylation of protein in intact cells was inhibited by Ebselen (IC50 ca. 50 .mu.M). These pharmacodynamic properties of Ebselen are discussed in terms of its anti-inflammatory activity in vivo. The findings are also discussed in terms of Ebselen''s known ability to interact with sulfhydryl components of cells, particularly critical thiol components of the enzymes studied.