Apocynin prevents cyclooxygenase 2 expression in human monocytes through NADPH oxidase and glutathione redox-dependent mechanisms
Apocynin prevents cyclooxygenase 2 expression in human monocytes through NADPH oxidase and glutathione redox-dependent mechanisms
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DOI：
10.1016/j.freeradbiomed.2004.04.020
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发表时间：
2004-07-15
影响因子：
7.4
通讯作者：
Colli, S
中科院分区：
文献类型：
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作者：
Barbieri, SS;Cavalca, V;Colli, S
在本研究中，我们报告了apocynin，喜马拉雅草药胡黄连的活性成分，对环氧合酶-2（考克斯-2）的合成和活性的人粘附单核细胞暴露于血清处理的酵母聚糖（STZ）和佛波醇肉豆蔻酸酯（PMA）的预防作用。夹竹桃麻素显著降低细胞内还原型/氧化型谷胱甘肽比值（GSH/GSSG）并阻止受刺激单核细胞中核因子-κ B（NF-κ B）的活化。此外，它减少了细胞内活性氧（ROS）的产生，单核细胞匀浆中NADPH氧化酶的活性和单核细胞膜中p47（phox）亚基的转位。在夹竹桃素处理的单核细胞的裂解物中p47（phox）水平也降低。夹竹桃麻素对考克斯-2的抑制作用被GSH完全消除。该研究的结果表明，夹竹桃麻素抑制单核细胞中由增加的氧化张力诱导的考克斯-2合成和活性，并为该化合物在许多细胞和动物炎症模型中发挥的保护作用提供了解释。NADPH氧化酶衍生的ROS的衰减与GSH/GSSG减少和NF-κ B活化的抑制相结合被强调为负责考克斯-2抑制的分子机制。(C)2004年爱思唯尔公司All rights reserved.
In the present study we report the preventive effect of apocynin, an active constituent of the Himalayan herb Picrorhiza kurrooa, on cyclooxygenase-2 (Cox-2) synthesis and activity in human adherent monocytes exposed to serum treated zymosan (STZ) and phorbol myristate acetate (PMA). Apocynin markedly decreases the intracelludar reduced/oxidized glutathione ratio (GSH/GSSG) and prevents nuclear factor-kappaB (NF-kappaB) activation in stimulated monocytes. Moreover, it reduces intracellular reactive oxygen species (ROS) generation, NADPH oxidase activity in monocyte homogenates and translocation of p47(phox) subunit in monocyte membranes. p47(phox) levels are also reduced in lysates of apocynin-treated monocytes. The inhibition of Cox-2 by apocynin is completely abrogated by GSH provision. Results from this study indicate that apocynin inhibits Cox-2 synthesis and activity induced in monocytes by an increased oxidative tone and provide an explanation for the protective effect exerted by this compound in numerous cell and animal models of inflammation. Attenuation of NADPH oxidase derived ROS coupled with GSH/GSSG reduction and suppression of NF-kappaB activation are highlighted as the molecular mechanisms responsible for Cox-2 inhibition. (C) 2004 Elsevier Inc. All rights reserved.