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

醌类化合物引起环境颗粒物污染氧化应激的生物学效应

• 批准号: 15390184
• 负责人: KUMAGAI Yoshito
• 金额: $ 9.66万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390184/
• 关键词: diesel exhaust particles; polycyclic aromatic hydrocarbon quinines; oxidative stress; covalent attachment; vasorelaxation; tracheal contraction; 一酸化窒素; ディーゼル排出粒子; 大気中ナノ粒子; 血管収縮

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

我们发现，9，10-菲醌（9，10-PQ）是柴油机尾气颗粒物（DEP）和大气PM2.5中污染的一种丰富的醌，1，2-萘醌（1，2-NQ）被鉴定为DEP和大气PM2.5中的一种环境醌。已知这种多环芳烃奎宁容易与亲核试剂如蛋白质SH官能团反应，引起关键细胞蛋白质的烷基化。另外，9，10-PQ和1，2-NQ是高度氧化还原活性的分子，可参与其半醌自由基阴离子的氧化还原循环，导致活性氧物质的形成。9，10-PQ腔内注射后48小时（1 μg/只）给药后，9，10-PQ暴露动物支气管肺泡灌洗液中的中性粒细胞和嗜酸性粒细胞水平远高于对照小鼠。此时巨噬细胞水平未受影响。我们的研究结果表明，PQ可能通过抑制细胞因子/趋化因子的表达而增加细胞因子/趋化因子。 ...更多信息 离体研究：1，2-NQ引起主动脉环中乙酰胆碱诱导的内皮依赖性血管舒张的显著抑制，表明1，2-NQ是抑制eNOS活性的环境醌，从而破坏NO依赖性血管张力。1，2-NQ对豚鼠气管平滑肌有浓度依赖性收缩作用，EC_（50）为18.7 μM。从几条证据表明，1，2-NQ介导的气管收缩至少部分归因于激活辣椒素受体的蛋白酪氨酸激酶磷酸化，导致平滑肌细胞中细胞内钙含量增加。当我们检测9，10-PQ对A549人肺上皮细胞的影响时，9，10-PQ诱导细胞凋亡，LC 50为0.77 μM。在用9，10-PQ处理后的细胞中也检测到蛋白质羰基的形成DNA片段，这表明9，10-PQ诱导氧化蛋白质损伤，导致凋亡。少

项目成果

Complementary DNA microarray analysis in acute lung injury induced by lipopolysaccharide and diesel exhaust particles

脂多糖和柴油机尾气颗粒诱导的急性肺损伤的互补DNA微阵列分析

• 发表时间: 2004
• 期刊: Exp Biol Med 229
• 作者: Yanagisawa R;Takano H;et al.
• 通讯作者: et al.

9,10-phenanthraquinone in diesel exhaust downregulates HO-1 and Cu, Zn-SOD in human pulmonary epithelial cells : intracellular iron scavenger 1,10-phenanthroline affords protection against apoptosis.

柴油机尾气中的 9,10-菲醌下调人肺上皮细胞中的 HO-1 和 Cu, Zn-SOD：细胞内铁清除剂 1,10-菲咯啉可防止细胞凋亡。

• 发表时间: 2005
• 期刊: Free Radical Biology & Medicine 38
• 作者: Sugimoto R;Kumagai Y;Nakai Y;Ishii T
• 通讯作者: Ishii T

Yanagisavva, R., et al.: "Enhancement of acute lung injury related to bacterial endotoxin by components of diesel exhaust particles"Thorax. 58. 605-612 (2003)

Yanagisavva, R. 等人：“柴油机尾气颗粒成分增强与细菌内毒素相关的急性肺损伤”胸部。

1,2-naphthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea

• DOI: 10.1016/j.taap.2005.06.015
• 发表时间: 2006-01-01
• 期刊: TOXICOLOGY AND APPLIED PHARMACOLOGY
• 影响因子: 3.8
• 作者: Kikuno, S;Taguchi, K;Kumagai, Y
• 通讯作者: Kumagai, Y

Redox activity of airborne particulate matter at different sites in the Los Angels Basin.

洛杉矶盆地不同地点空气中颗粒物的氧化还原活动。

• 发表时间: 2005
• 期刊: Environmental Research 99
• 作者: Cho AK;Sioutas C;Miguel AH;Kumagai Y;Schmitz DA;Singh M;Eiguren-Fernandez A;Froines JR
• 通讯作者: Froines JR