Kafoury Ramzi M, Huang Ming-Ju
Center for Environmental Health, College of Science, Engineering, and Technology, Jackson State University, Jackson, Mississippi 39217, USA.
Environ Toxicol. 2005 Aug;20(4):441-8. doi: 10.1002/tox.20130.
The sequence of events leading to ozone-induced airway inflammation is not well known. To elucidate the molecular and cellular events underlying ozone toxicity in the lung, we hypothesized that lipid ozonation products (LOPs) generated by the reaction of ozone with unsaturated fatty acids in the epithelial lining fluid and cell membranes play a key role in mediating ozone-induced airway inflammation. To test our hypothesis, we ozonized 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) and generated LOPs. Confluent human bronchial epithelial cells were exposed to the derivatives of ozonized POPC-9-oxononanoyl, 9-hydroxy-9-hydroperoxynonanoyl, and 8-(5-octyl-1,2,4-trioxolan-3-yl-)octanoyl-at a concentration of 10 muM, and the activity of phospholipases A2 (PLA2), C (PLC), and D (PLD) was measured (1, 0.5, and 1 h, respectively). Quantitative structure-activity relationship (QSAR) models were utilized to predict the biological activity of LOPs in airway epithelial cells. The QSAR results showed a strong correlation between experimental and computed activity (r = 0.97, 0.98, 0.99, for PLA2, PLC, and PLD, respectively). The results indicate that QSAR models can be utilized to predict the biological activity of the various ozone-derived LOP species in the lung.
导致臭氧诱导气道炎症的一系列事件尚不清楚。为了阐明肺部臭氧毒性背后的分子和细胞事件，我们推测臭氧与上皮衬液和细胞膜中的不饱和脂肪酸反应产生的脂质臭氧化产物（LOPs）在介导臭氧诱导的气道炎症中起关键作用。为了验证我们的假设，我们对1-棕榈酰-2-油酰基-sn-甘油-3-磷脂酰胆碱（POPC）进行臭氧化处理并生成LOPs。将汇合的人支气管上皮细胞暴露于浓度为10 μM的臭氧化POPC的衍生物——9-氧代壬酰基、9-羟基-9-氢过氧壬酰基和8-（5-辛基-1,2,4-三氧杂环戊烷-3-基）辛酰基——下，并分别在1、0.5和1小时后测量磷脂酶A2（PLA2）、C（PLC）和D（PLD）的活性。利用定量构效关系（QSAR）模型预测LOPs在气道上皮细胞中的生物活性。QSAR结果显示实验活性与计算活性之间存在很强的相关性（PLA2、PLC和PLD的r分别为0.97、0.98、0.99）。结果表明，QSAR模型可用于预测肺部各种臭氧衍生的LOP物种的生物活性。
