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双酚 A 暴露改变了人视网膜母细胞瘤 Y79 细胞的转录组和蛋白质组动态。

Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells.

机构信息

Department of Life Science, Chung-Ang University, Seoul 06974, Korea.

出版信息

Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.

Abstract

Bisphenol A (BPA) is a xenoestrogen chemical commonly used to manufacture polycarbonate plastics and epoxy resin and might affect various human organs. However, the cellular effects of BPA on the eyes have not been widely investigated. This study aimed to investigate the cellular cytotoxicity by BPA exposure on human retinoblastoma cells. BPA did not show cytotoxic effects, such as apoptosis, alterations to cell viability and cell cycle regulation. Comparative analysis of the transcriptome and proteome profiles were investigated after long-term exposure of Y79 cells to low doses of BPA. Transcriptome analysis using RNA-seq revealed that mRNA expression of the post-transcriptional regulation-associated gene sets was significantly upregulated in the BPA-treated group. Cell cycle regulation-associated gene sets were significantly downregulated by exposure to BPA. Interestingly, RNA-seq analysis at the transcript level indicated that alternative splicing events, particularly retained introns, were noticeably altered by low-dose BPA treatment. Additionally, proteome profiling using MALDI-TOF-MS identified a total of nine differentially expressed proteins. These results suggest that alternative splicing events and altered gene/protein expression patterns are critical phenomena affected by long-term low-dose BPA exposure. This represents a novel marker for the detection of various diseases associated with environmental pollutants such as BPA.

摘要

双酚 A(BPA)是一种常用的异雌激素化学物质,用于制造聚碳酸酯塑料和环氧树脂,可能会影响人体的各种器官。然而,BPA 对眼睛的细胞影响尚未得到广泛研究。本研究旨在探讨 BPA 暴露对人视网膜母细胞瘤细胞的细胞毒性。BPA 并未显示出细胞毒性作用,如凋亡、细胞活力改变和细胞周期调节。对 Y79 细胞进行长期低剂量 BPA 暴露后,对转录组和蛋白质组谱进行了比较分析。使用 RNA-seq 的转录组分析显示,BPA 处理组中转录后调控相关基因集的 mRNA 表达显著上调。BPA 暴露使细胞周期调控相关基因集显著下调。有趣的是,基于转录水平的 RNA-seq 分析表明,低剂量 BPA 处理明显改变了选择性剪接事件,特别是保留的内含子。此外,使用 MALDI-TOF-MS 的蛋白质组分析共鉴定出 9 种差异表达蛋白。这些结果表明,选择性剪接事件和基因/蛋白质表达模式的改变是受长期低剂量 BPA 暴露影响的关键现象。这代表了一种用于检测与 BPA 等环境污染物相关的各种疾病的新型标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a18b/7918513/3e19f29516d4/genes-12-00264-g001.jpg

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