Biological effect of quinoid compounds causing oxidative stress contaminated in ambient particulate matter

研究发现，9，10-菲醌(9，10-PQ)是柴油车尾气颗粒物(DEP)和大气PM2.5中含量丰富的一种对苯二酚，1，2-萘酚(1，2-NQ)是柴油车尾气颗粒物(DEP)和大气PM2.5中的环境对苯二酚。众所周知，这种多环芳烃奎宁很容易与亲核性物质如蛋白质SH发生反应，导致关键细胞蛋白质的烷基化。另外，9，10-PQ和1，2-NQ是高度氧化还原的活性分子，可以与它们的半喹酮阴离子一起参与氧化还原循环，导致活性氧物种的形成。体内研究：小鼠气管内注射9，10-PQ(1μg/只)48小时后，暴露于9，10-PQ的小鼠支气管肺泡灌洗液中中性粒细胞和嗜酸性粒细胞的水平远远高于对照组小鼠。巨噬细胞的水平目前没有受到影响。我们的结果提示PQ可能通过前…增加细胞因子/趋化因子。体外研究：1，2-NQ可显著抑制Ach诱导的内皮依赖性血管松弛作用，提示1，2-NQ是一种环境对苯二酚，可抑制eNOS活性，从而破坏NO依赖的血管张力。1，2-NQ能引起浓度依赖性的豚鼠气管平滑肌收缩，EC50值为18.7μM。多项证据表明，1，2-NQ介导的气管收缩至少部分归因于蛋白酪氨酸激酶磷酸化，激活辣椒素受体，导致细胞内钙含量增加。培养细胞研究：当我们检测9，10-PQ对人肺上皮细胞A549的影响时，9，10-PQ诱导了A549人肺上皮细胞的凋亡，LC_(50)为~7μM。导致细胞凋亡。较少

We found that 9,10-phenanthraquinone (9,10-PQ) is an abundant quinone in contaminated in diesel exhaust particles (DEP) and atmospheric PM2.5 and that 1,2-Naphthoquinone (1,2-NQ) is identified as an environmental quinone in DEP and atmospheric PM2.5. Such polycyclic aromatic hydrocarbon quinines are known to react readily with nucleophiles such as protein SH functions to cause alkylation of crucial cellular proteins. Alternatively, 9,10-PQ and 1,2-NQ are highly redox active molecules that can be involved in the redox cycle with their semiquinone radical anions, resulting in the formation of reactive oxygen species.In vivo study : Forty eight hours after intratracheal injection of 9,10-PQ (1 μg/body) into mice, levels of neutrophils and eosinophils, in the bronchial alveolar lavage from 9,10-PQ exposed animals were much greater than those from control mice. Levels of macrophages were not affected at this time. Our results suggest that PQ may increase the cytokine/chemokine through presu … More mably Th2 activation, thereby causing elevated BAL levels of neutrophils and eosinophils associated with inflammation.Ex vivo studies : 1,2-NQ caused a significant suppression of Ach-induced endothelium-dependent vasorelaxation in aortic ring, suggesting that 1,2-NQ is an environmental quinone that inhibits eNOS activity, thereby disrupting NO-dependent vascular tone. 1,2-NQ is capable of causing a concentration dependent contraction of tracheal smooth muscle in guinea pigs with EC50 value of 18.7 μM. From several lines of evidence suggested that 1,2-NQ-mediated tracheal contraction was, at least in part, attributable to protein tyrosone kinasess phosphorylation that activates capsaicin receptor, resulting in increased intracellular calcium content in the smooth muscle cells.Cultured cells study : When we examined the effects of 9,10-PQ on A549 human pulmonary epithelial cells, 9,10-PQ induced apoptosis with a LC5O of 〜7 μM. Formation of protein carbonyls DNA fragmentation were also detected in cells after treatment with 9,10-PQ, suggesting that 9,10-PQ induces oxidative protein damage, leading to apoptosis. Less