Ambient vapor samples activate the Nrf2-ARE pathway in human bronchial epithelial BEAS-2B cells.

Ambient vapor samples activate the Nrf2-ARE pathway in human bronchial epithelial BEAS-2B cells.
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DOI:
10.1002/tox.21860
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发表时间:
2014-11
影响因子:
4.5
通讯作者:
Kumagai, Yoshito
Kumagai, Yoshito
中科院分区:
医学3区
文献类型:
--
作者:
Shinkai, Yasuhiro;Nakajima, Syun;Eiguren-Fernandez, Arantza;Di Stefano, Emma;Schmitz, Debra A.;Froines, John R.;Cho, Arthur K.;Kumagai, Yoshito

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环境空气污染物已被报道在人类和实验动物中诱导基于氧化应激的炎症反应。然而,这些报告大多描述了环境样品和废气样品中颗粒物相的行为。我们在这里介绍了使用DNA微阵列分析在洛杉矶市中心地区收集的环境空气样本的汽相对人支气管上皮BEAS-2B细胞的作用的研究结果。在表达增加4倍或更多的26个基因中,有4个基因与转录因子Nrf2调控的解毒基因相关。与这些结果一致的是,蒸汽样品激活了Nrf2-ARE途径,导致血红素加氧酶-1(HO-1)、谷氨酸半胱氨酸连接酶修饰子亚单位和半胱氨酸转运蛋白(XCT)的mRNA和蛋白上调。没有观察到致炎基因的明显增加。这些结果表明,环境蒸汽样本激活了Nrf2-Are途径,但不是炎症反应。此外,用谷胱甘肽处理蒸气样品导致Nrf2激活和HO-1诱导减少,这表明蒸气样品中的亲电体有助于这种依赖Nrf2的抗氧化剂或适应性反应。
Ambient air pollutants have been reported to induce oxidative stress based inflammatory responses in humans and experimental animals. However, most of these reports describe the actions of the particulate phase of ambient and exhaust samples. We describe here results of studies investigating the actions of the vapor phase of ambient air samples collected in the midtown area of Los Angeles on human bronchial epithelial BEAS-2B cells using DNA microarray analysis. Among 26 genes whose expression increased fourfold or more, four genes were associated with detoxifying genes regulated by the transcription factor Nrf2. Consistent with these results, the vapor samples activate the Nrf2-ARE pathway, resulting in up-regulation of heme oxygenase-1 (HO-1), glutamate cysteine ligase modifier subunit, and cystine transporter (xCT) mRNA and proteins. No appreciable increases in pro-inflammatory genes were observed. These results suggest that ambient vapor samples activate the Nrf2-ARE pathway but not an inflammatory response. Also, treatment of the vapor samples with glutathione resulted in reduction in the Nrf2 activation and HO-1 induction, suggesting that electrophiles in vapor samples contribute to this Nrf2-dependent antioxidant or adaptive response.
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