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醌类物质联合加热 PM2.5 和/或亚洲沙尘暴露对人呼吸道上皮细胞细胞死亡和 ROS 产生的差异模式。

Differential Pattern of Cell Death and ROS Production in Human Airway Epithelial Cells Exposed to Quinones Combined with Heated-PM2.5 and/or Asian Sand Dust.

机构信息

Graduate School of Engineering, Kyoto University, Kyoto 615-8540, Japan.

School of Nursing, University of Shizuoka, Shizuoka 422-8526, Japan.

出版信息

Int J Mol Sci. 2023 Jun 23;24(13):10544. doi: 10.3390/ijms241310544.

Abstract

The combined toxicological effects of airborne particulate matter (PM), such as PM2.5, and Asian sand dust (ASD), with surrounding chemicals, particularly quinones, on human airway epithelial cells remain underexplored. In this study, we established an in vitro combination exposure model using 1,2-naphthoquinones (NQ) and 9,10-phenanthroquinones (PQ) along with heated PM (h-PM2.5 and h-ASD) to investigate their potential synergistic effects. The impacts of quinones and heated PM on tetrazolium dye (WST-1) reduction, cell death, and cytokine and reactive oxygen species (ROS) production were examined. Results revealed that exposure to 9,10-PQ with h-PM2.5 and/or h-ASD dose-dependently increased WST-1 reduction at 1 μM compared to the corresponding control while markedly decreasing it at 10 μM. Higher early apoptotic, late apoptotic, or necrotic cell numbers were detected in 9,10-PQ + h-PM2.5 exposure than in 9,10-PQ + h-ASD or 9,10-PQ + h-PM2.5 + h-ASD. Additionally, 1,2-NQ + h-PM2.5 exposure also resulted in an increase in cell death compared to 1,2-NQ + h-ASD and 1,2-NQ + h-PM2.5 + h-ASD. Quinones with or without h-PM2.5, h-ASD, or h-PM2.5 + h-ASD significantly increased ROS production, especially with h-PM2.5. Our findings suggest that quinones, at relatively low concentrations, induce cell death synergistically in the presence of h-PM2.5 rather than h-ASD and h-PM2.5 + h-ASD, partially through the induction of apoptosis with increased ROS generation.

摘要

空气中的颗粒物(PM),如 PM2.5,和亚洲沙尘(ASD)与周围化学物质,特别是醌类物质,对人体气道上皮细胞的联合毒理学效应仍未得到充分研究。在这项研究中,我们建立了一种体外联合暴露模型,使用 1,2-萘醌(NQ)和 9,10-菲醌(PQ)以及加热的 PM(h-PM2.5 和 h-ASD),以研究它们的潜在协同作用。研究了醌类物质和加热的 PM 对四唑染料(WST-1)还原、细胞死亡以及细胞因子和活性氧(ROS)产生的影响。结果表明,与相应的对照相比,暴露于 9,10-PQ 与 h-PM2.5 和/或 h-ASD 剂量依赖性地增加了 1 μM 时的 WST-1 还原,但在 10 μM 时明显降低了 WST-1 还原。与 9,10-PQ + h-ASD 或 9,10-PQ + h-PM2.5 + h-ASD 相比,在 9,10-PQ + h-PM2.5 暴露下检测到更高的早期凋亡、晚期凋亡或坏死细胞数量。此外,与 1,2-NQ + h-ASD 和 1,2-NQ + h-PM2.5 + h-ASD 相比,1,2-NQ + h-PM2.5 暴露也导致细胞死亡增加。有或没有 h-PM2.5、h-ASD 或 h-PM2.5 + h-ASD 的醌类物质显著增加了 ROS 的产生,特别是在 h-PM2.5 存在的情况下。我们的研究结果表明,醌类物质在相对较低的浓度下,在存在 h-PM2.5 的情况下协同诱导细胞死亡,而不是 h-ASD 和 h-PM2.5 + h-ASD,部分通过诱导细胞凋亡和增加 ROS 生成来实现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9a/10341977/934a6908d8e0/ijms-24-10544-g001.jpg

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