Miyaura S, Eguchi H, Johnston J M
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9038.
Circ Res. 1992 Feb;70(2):341-7. doi: 10.1161/01.res.70.2.341.
Cigarette smoking is associated with an increased incidence of a number of diseases. Minimal information is available at the molecular level concerning the mechanism of action of cigarette smoke. Platelet-activating factor (PAF) is one of the most potent proinflammatory agents described. PAF concentration may be regulated by the degradation of PAF as catalyzed by the plasma enzyme, PAF acetylhydrolase (PAF-AH). This enzyme is associated with the lipoprotein fraction. The exposure of low density lipoprotein to a cigarette smoke extract (CSE) has been shown to alter the charge of low density lipoprotein and its uptake by macrophages. The activity of PAF-AH in the lipoprotein fraction has been assayed after exposure to CSE. The activity of PAF-AH was inhibited by the CSE in a dose-dependent manner. The inhibition of PAF-AH by the CSE was not altered by superoxide dismutase or catalase addition. Sulfhydryl compounds prevented and reversed the inhibition of PAF-AH caused by CSE. The inhibitor present in CSE was not nicotine, its major metabolic product, (-)-cotinine, or several compounds known to be present in the extract. The charge alteration reaction(s) and PAF-AH inhibition appear to be localized at different sites of the lipoprotein molecule. The observed inhibition may account for the increase in the plasma PAF concentration that is known to occur in smokers. The increase of PAF may contribute to the increased incidence of cardiovascular and lung diseases known to be present in smokers.
吸烟与多种疾病发病率的增加有关。在分子水平上，关于香烟烟雾作用机制的信息极少。血小板活化因子（PAF）是所描述的最有效的促炎剂之一。PAF的浓度可能受血浆酶PAF乙酰水解酶（PAF-AH）催化的PAF降解作用调节。这种酶与脂蛋白部分相关。已有研究表明，低密度脂蛋白暴露于香烟烟雾提取物（CSE）会改变其电荷以及巨噬细胞对其的摄取。在暴露于CSE后，对脂蛋白部分中的PAF-AH活性进行了测定。CSE以剂量依赖的方式抑制PAF-AH的活性。添加超氧化物歧化酶或过氧化氢酶不会改变CSE对PAF-AH的抑制作用。巯基化合物可预防并逆转CSE对PAF-AH的抑制作用。CSE中的抑制剂不是尼古丁、其主要代谢产物（-）-可替宁，也不是提取物中已知存在的几种化合物。电荷改变反应和PAF-AH抑制作用似乎定位于脂蛋白分子的不同位点。观察到的抑制作用可能解释了吸烟者血浆中已知会升高的PAF浓度。PAF的升高可能导致吸烟者中已知存在的心血管疾病和肺部疾病发病率增加。
