Polyphenol cytotoxicity induced by the bacterial toxin pyocyanin: role of NQO1
Polyphenol cytotoxicity induced by the bacterial toxin pyocyanin: role of NQO1
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DOI：
10.1016/j.freeradbiomed.2009.04.011
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发表时间：
2009-07-01
影响因子：
7.4
通讯作者：
Muller, Michael
中科院分区：
文献类型：
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作者：
Muller, Michael
绿脓素是一种重要的细菌氧化还原活性毒素，由机会性人类病原体铜绿假单胞菌产生。这种细菌是导致呼吸道严重感染的原因，特别是对于囊性纤维化患者和烧伤患者。绿脓素会诱发氧化应激，导致细胞过早衰老，从而损害组织重塑和伤口修复。人们发现多种抗氧化剂可有效预防氧化剂诱导的细胞衰老，其中包括槲皮素（一种常见的膳食多酚）。这项研究评估了三种常见多酚（槲皮素、(+)-儿茶素和 (-)-表儿茶素）作为绿脓素诱导衰老的潜在抑制剂的有效性。虽然在最低浓度下，多酚保持了细胞复制能力，但在绿脓素存在下，它们出乎意料地表现出浓度依赖性细胞毒性，排序顺序为槲皮素>表儿茶素>>儿茶素。氧化时，具有 B 环儿茶酚功能的多酚会形成有毒的烷基化醌，通常会被细胞抗氧化防御和氧化还原维持系统灭活，包括抗坏血酸和 NAD(P)H:醌氧化还原酶 1 (NQO1) 的还原。绿脓素在低微摩尔浓度下抑制细胞 NQO1 活性，但外源抗坏血酸的存在消除了绿脓素诱导的多酚细胞毒性。这些数据表明绿脓素会损害细胞氧化还原维持系统，使细胞容易受到其他无毒氧化还原活性化合物的不利影响。 (C) 2009 Elsevier Inc. 保留所有权利。
Pyocyanin is an important bacterial redox-active toxin produced by the opportunistic human pathogen Pseudomonas aeruginosa. The bacterium is a cause of serious infections of the respiratory tract, particularly for those with cystic fibrosis and for those with burn injuries. Pyocyanin induces oxidative stress and causes cells to become prematurely senescent, which compromises tissue remodeling and wound repair. A diverse range of antioxidants have been found useful in preventing oxidant-induced cellular senescence, including quercetin, a common dietary polyphenol. This study evaluated the effectiveness of three common polyphenols (quercetin, (+)-catechin, and (-)-epicatechin) as potential inhibitors of pyocyanin-induced senescence. Whereas at the lowest concentration the polyphenols maintained cellular replicative capacity, in the presence of pyocyanin they unexpectedly displayed concentration-dependent cytotoxicity with a rank order of quercetin>epicatechin>>catechin. On oxidation, polyphenols with B-ring catechol functionality form toxic alkylating quinones that are normally inactivated by cellular antioxidant defense and redox maintenance systems, including reduction by ascorbate and NAD(P)H:quinone oxidoreductase 1 (NQO1). Pyocyanin inhibited cellular NQO1 activity at low micromolar concentrations, but the presence of exogenous ascorbate eliminated pyocyanin-induced polyphenol cytotoxicity. These data indicate that pyocyanin compromises cellular redox maintenance systems, leaving cells susceptible to the adverse effects of otherwise nontoxic redox-active compounds. (C) 2009 Elsevier Inc. All rights reserved.