PM2.5 暴露对人脐静脉内皮细胞时钟基因 BMAL1 和细胞周期的影响

IF 2.2 4区 医学 Q3 TOXICOLOGY Toxicology Research Pub Date : 2024-02-26 eCollection Date: 2024-02-01 DOI:10.1093/toxres/tfae022
Haochong Shen, Meidi Gong, Minghao Zhang, Shikun Sun, Rao Zheng, Qing Yan, Juan Hu, Xiaobin Xie, Yan Wu, Junjie Yang, Jing Wu, Jing Yang
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引用次数: 0

摘要

背景:细颗粒物(PM2.5)暴露与心血管疾病密切相关,而心血管疾病与细胞周期停滞有关。脑和肌肉芳香烃受体核转运体样蛋白1(BMAL1)不仅参与调节昼夜节律,还在调节细胞周期方面发挥作用。然而,昼夜节律钟基因 BMAL1 对 PM2.5 诱导的细胞周期变化的确切贡献仍不清楚。本研究旨在探讨 PM2.5 暴露对 BMAL1 表达和人脐静脉内皮细胞(HUVECs)细胞周期的影响。方法:将 HUVECs 暴露于不同浓度(0、12.5、25、75 和 100 μg.mL-1)的 PM2.5 24 小时,以阐明其潜在的毒性机制。暴露于 PM2.5 后,检测了细胞活力、ROS、细胞周期以及关键基因和蛋白质的表达:结果:在暴露于 PM2.5 的 HUVECs 中观察到细胞活力明显下降,ROS 生成显著增加。此外,PM2.5 暴露的 HUVEC 细胞周期停滞在 G0/G1 期,p27 的基因表达也明显增加。BMAL1 的蛋白表达和基因表达均显著增加。此外,PM2.5 暴露的 HUVEC 中 p-p38 MAPK 和 p-ERK1/2 的蛋白表达量也明显增加。此外,在用 siBMAL1 转染 HUVEC 以抑制 BMAL1 的表达后,我们观察到暴露于 PM2.5 的 HUVEC 中 MAPK/ERK 通路的蛋白和基因表达均有所减少:总之,我们的研究结果表明,PM2.5暴露会显著上调BMAL1的昼夜节律钟基因表达,并通过MAPK/ERK通路调控HUVECs的G0/G1细胞周期停滞,这可能会为BMAL1关于PM2.5诱发心血管疾病的潜在分子机制提供新的见解。
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Effects of PM2.5 exposure on clock gene BMAL1 and cell cycle in human umbilical vein endothelial cells.

Background: Fine particulate matter (PM2.5) exposure has been closely associated with cardiovascular diseases, which are relevant to cell cycle arrest. Brain and muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) not only participates in regulating the circadian clock but also plays a role in modulating cell cycle. However, the precise contribution of the circadian clock gene BMAL1 to PM2.5-induced cell cycle change remains unclear. This study aims to explore the impact of PM2.5 exposure on BMAL1 expression and the cell cycle in human umbilical vein endothelial cells (HUVECs).

Methods: HUVECs was exposed to PM2.5 for 24 hours at different concentrations ((0, 12.5, 25, 75 and 100 μg.mL-1) to elucidate the potential toxic mechanism. Following exposure to PM2.5, cell viability, ROS, cell cycle, and the expression of key genes and proteins were detected.

Results: A remarkable decrease in cell viability is observed in the PM2.5-exposed HUVECs, as well as a significant increase in ROS production. In addition, PM2.5-exposed HUVECs have cycle arrest in G0/G1 phase, and the gene expression of p27 is also markedly increased. The protein expression of BMAL1 and the gene expression of BMAL1 are increased significantly. Moreover, the protein expressions of p-p38 MAPK and p-ERK1/2 exhibit a marked increase in the PM2.5-exposed HUVECs. Furthermore, following the transfection of HUVECs with siBMAL1 to suppress BMAL1 expression, we observed a reduction in both the protein and gene expression of the MAPK/ERK pathway in HUVECs exposed to PM2.5.

Conclusions: Overall, our results indicate that PM2.5 exposure significantly upregulates the circadian clock gene expression of BMAL1 and regulates G0/G1 cell cycle arrest in HUVECs through the MAPK/ERK pathway, which may provide new insights into the potential molecular mechanism regarding BMAL1 on PM2.5-induced cardiovascular diseases.

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来源期刊
Toxicology Research
Toxicology Research TOXICOLOGY-
CiteScore
3.60
自引率
0.00%
发文量
82
期刊介绍: A multi-disciplinary journal covering the best research in both fundamental and applied aspects of toxicology
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