Leikauf G D, Zhao Q, Zhou S, Santrock J
Department of Environmental Health, University of Cincinnati Medical Center, Ohio 45267-0056.
Am J Respir Cell Mol Biol. 1993 Dec;9(6):594-602. doi: 10.1165/ajrcmb/9.6.594.
When inhaled, ozone reacts at the airway luminal surface with unsaturated fatty acids contained in the extracellular fluid and plasma membrane to form an aldehyde and hydroxyhydroperoxide. The resulting hydroxyhydroperoxide degrades in aqueous systems to yield a second aldehyde and hydrogen peroxide (H2O2). Previously, we demonstrated that ozone can augment eicosanoid metabolism in bovine airway epithelial cells. To examine structure-activity relationships of ozone-fatty acid degradation products on eicosanoid metabolism in human airway epithelial cells, 3-, 6-, and 9-carbon saturated aldehydes and hydroxyhydroperoxides were synthesized and purified. Eicosanoid metabolism was evaluated by determination of total 3H-activity release from confluent cells previously incubated with [3H]arachidonic acid and by identification of specific metabolites with high performance liquid chromatography and radioimmunoassay. The major metabolites detected were prostaglandin E2, prostaglandin F2 alpha, and 15-hydroxyeicosatetraenoic acid. The 9-carbon aldehyde, nonanal, in contrast to 3- or 6-carbon aldehydes, stimulated release at concentrations > or = 100 microM, suggesting that the stimulatory effect increases with increasing chain length. When tested under identical conditions, the 3-, 6-, and 9-carbon hydroxyhydroperoxides were more potent than the corresponding aldehydes. Again, a greater effect was noted when the chain length was increased. One possible explanation for the increased potency of the hydroxyhydroperoxides over the aldehydes could be due to degradation of the hydroxyhydroperoxide into H2O2 and aldehyde. We consider this an unlikely explanation because responses varied with chain length (although each hydroxyhydroperoxide would produce an equivalent amount of H2O2) and because exposure to H2O2 alone or H2O2 plus hexanal produced a response dissimilar to 1-hydroxy-1-hexanehydroperoxide.(ABSTRACT TRUNCATED AT 250 WORDS)
吸入时，臭氧在气道腔表面与细胞外液和质膜中所含的不饱和脂肪酸发生反应，形成醛和羟基氢过氧化物。生成的羟基氢过氧化物在水性体系中降解，产生第二种醛和过氧化氢（H2O2）。此前，我们证明臭氧可增强牛气道上皮细胞中的类花生酸代谢。为研究臭氧 - 脂肪酸降解产物对人气道上皮细胞类花生酸代谢的构效关系，合成并纯化了3碳、6碳和9碳的饱和醛和羟基氢过氧化物。通过测定先前用[3H]花生四烯酸孵育的汇合细胞中总3H活性释放，并通过高效液相色谱和放射免疫测定法鉴定特定代谢产物，来评估类花生酸代谢。检测到的主要代谢产物为前列腺素E2、前列腺素F2α和15 - 羟基二十碳四烯酸。与3碳或6碳醛相比，9碳醛壬醛在浓度≥100μM时刺激释放，表明刺激作用随链长增加而增强。在相同条件下测试时，3碳、6碳和9碳的羟基氢过氧化物比相应的醛更有效。同样，链长增加时效果更明显。羟基氢过氧化物比醛效力增加的一个可能解释可能是羟基氢过氧化物降解为H2O2和醛。我们认为这不是一个合理的解释，因为反应随链长而变化（尽管每种羟基氢过氧化物会产生等量的H2O2），并且因为单独暴露于H2O2或H2O2加己醛产生的反应与1 - 羟基 - 1 - 己烷氢过氧化物不同。（摘要截取自250字）
