Yu Jingjing, Weïwer Michel, Linhardt Robert J, Dordick Jonathan S
Department of Biology, Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Curr Vasc Pharmacol. 2008 Jul;6(3):204-17. doi: 10.2174/157016108784911984.
Oxidative stress has been linked to the origin and progression of cardiovascular diseases. Nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase is a multi-component, NADPH-dependent enzyme that generates superoxide anion in the presence of molecular oxygen. The enzyme has been identified and characterized in all 3 vascular wall cell types and represents the major source of reactive oxygen species (ROS) production in the vascular wall. Inhibition of NADPH oxidase activation appears to suppress the sequence of cellular events that leads to a variety of cardiovascular diseases, including atherosclerosis. The naturally occurring methoxyphenol apocynin has been found to inhibit NADPH oxidase upon activation by peroxidases (e.g. soybean peroxidase, myeloperoxidase) or ROS under mild reaction conditions. Upon peroxidase-catalyzed activation, the apocynin oxidation products act to block the assembly and activation of NADPH oxidase. Although the mechanism of inhibition of NADPH oxidase remains largely unknown, apocynin's high effectiveness and low toxicity makes it a promising lead compound in the development of new therapeutic agents for cardiovascular diseases.
氧化应激与心血管疾病的发生和发展有关。还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶是一种多组分、依赖NADPH的酶，在有分子氧存在的情况下能产生超氧阴离子。该酶已在所有三种血管壁细胞类型中被鉴定和表征，是血管壁中活性氧（ROS）产生的主要来源。抑制NADPH氧化酶的激活似乎能抑制导致包括动脉粥样硬化在内的多种心血管疾病的细胞事件序列。已发现天然存在的甲氧基苯酚阿朴西林在过氧化物酶（如大豆过氧化物酶、髓过氧化物酶）或ROS激活下，在温和反应条件下可抑制NADPH氧化酶。在过氧化物酶催化的激活过程中，阿朴西林氧化产物可阻止NADPH氧化酶的组装和激活。尽管抑制NADPH氧化酶的机制在很大程度上仍不清楚，但阿朴西林的高效性和低毒性使其成为开发心血管疾病新治疗药物的有前景的先导化合物。
