Resveratrol prevents nanoparticles-induced inflammation and oxidative stress via downregulation of PKC-α and NADPH oxidase in lung epithelial A549 cells.
Resveratrol prevents nanoparticles-induced inflammation and oxidative stress via downregulation of PKC-α and NADPH oxidase in lung epithelial A549 cells.
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DOI：
10.1186/s12906-018-2278-6
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发表时间：
2018-07-09
影响因子：
--
通讯作者：
Lo YC
中科院分区：
文献类型：
--
作者：
Hsu HT;Tseng YT;Wong WJ;Liu CM;Lo YC
暴露于炭黑纳米颗粒（CBNPs），一种众所周知的工业生产，通过炎症和氧化应激促进肺毒性。最近的研究表明，一些多酚类物质通过调节蛋白激酶C-α（PKC-α）和NADPH氧化酶（Nox）信号通路发挥其抗氧化作用。白藜芦醇是水果中的一种膳食多酚，具有抗炎和抗氧化等多种保健作用。本研究旨在阐明PKC-α和Nox在CBNP诱导的人肺上皮A549细胞炎症和氧化应激中的作用，并探讨白藜芦醇对CBNP诱导的人肺上皮A549细胞炎症和氧化应激的保护作用。流式细胞仪检测细胞内活性氧（ROS）的产生和线粒体膜电位（Δ Δ Km）的变化。使用Griess试剂测量一氧化氮（NO），通过ELISA检测前列腺素E2（PGE 2）的产生，并通过Western印迹分析测量蛋白质表达。在肺上皮A549细胞中，CBNPs通过上调Nox 2和p67 phox的膜表达以及增加ROS产生来显著增强氧化应激。CBNPs还增加炎症因子，包括iNOS、考克斯-2、NO和PGE 2。白藜芦醇可减弱CBNPs对A549细胞的上述作用，并可诱导PKC-α的活化。我们发现PKC-α抑制剂（Gö 6976）可以通过下调A549细胞ROS、NO和PGE 2的产生来减轻CBNPs诱导的炎症反应，提示PKC-α可能参与了CBNPs诱导的氧化应激和炎症反应。我们的研究还发现白藜芦醇能够抑制CBNPs诱导的PKC-α蛋白表达。此外，ROS清除剂（NAC）和Nox抑制剂（DPI）减弱了CBNP诱导的iNOS和考克斯-2的表达。DPI还能抑制CBNPs诱导的ROS、NO和PGE 2的产生。白藜芦醇至少部分通过抑制PKC-α-和Nox相关信号转导来减弱CBNP诱导的肺上皮A549细胞中的氧化和炎症因子。
Exposure to carbon black nanoparticles (CBNPs), a well-known industrial production, promotes pulmonary toxicity through inflammation and oxidative stress. Recent studies show that some polyphenols exert their antioxidant properties through regulation of protein kinase C-α (PKC-α) and NADPH oxidase (Nox) signaling. Resveratrol, a dietary polyphenol in fruits, possesses various health beneficial effects including anti-inflammatory and antioxidative properties. In this study, we aimed to elucidate the involvement of PKC-α and Nox in CBNPs-induced inflammation and oxidative stress, and to investigate the protective effects of resveratrol on CBNP-induced inflammation and oxidative stress in human lung epithelial A549 cells. The production of reactive oxygen species (ROS) and the change of mitochondrial membrane potential (ΔΨm) were measured by flow cytometry. Nitric oxide (NO) was measured using the Griess reagent, and prostaglandin E2 (PGE2) production was detected by ELISA, while protein expressions were measured by Western blotting analysis. In lung epithelial A549 cells, CBNPs significantly enhanced oxidative stress by upregulation of Nox2 and membrane expression of p67phox accompanied with increase of ROS production. CBNPs also increased inflammatory factors, including iNOS, COX-2, NO and PGE2. However, resveratrol attenuated the above effects induced by CBNPs in A549 cells; additionally, CBNPs-induced activation of PKC-α was observed. We found that PKC-α inhibitor (Gö6976) could attenuate CBNPs-induced inflammation by down-regulation of ROS, NO and PGE2 production in A549 cells, suggesting PKC-α might be involved in CBNPs-induced oxidative stress and inflammation. Our results also found resveratrol was able to inhibit protein expression of PKC-α induced by CBNPs. Moreover, ROS scavenger (NAC) and Nox inhibitor (DPI) attenuated CBNPs-induced expressions of iNOS and COX-2. DPI could also attenuate CBNPs-induced ROS, NO and PGE2 production. Resveratrol attenuated CBNPs-induced oxidative and inflammatory factors in lung epithelial A549 cells, at least in part via inhibiting PKC-α- and Nox-related signaling.
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影响因子：
10
作者：
Jacobsen NR;Møller P;Jensen KA;Vogel U;Ladefoged O;Loft S;Wallin H
通讯作者：
Wallin H
多酚：对健康和衰老中心血管系统的好处。
影响因子：
5.9
作者：
Khurana S;Venkataraman K;Hollingsworth A;Piche M;Tai TC
通讯作者：
Tai TC
影响因子：
6.1
作者：
Aam, Berit Bjugan;Fonnum, F.
通讯作者：
Fonnum, F.
影响因子：
2.5
作者：
Kairisalo, Minna;Bonomo, Alessandra;Lindholm, Dan
通讯作者：
Lindholm, Dan
DOI：
10.1186/1478-811x-10-35
发表时间：
2012-11-23
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Lin CC;Hsieh HL;Shih RH;Chi PL;Cheng SE;Chen JC;Yang CM
通讯作者：
Yang CM