MCF-7 细胞衍生的外泌体通过转运功能参与保护源细胞免受三丁基氯化锡的损害。

IF 4.8 3区 医学 Q1 PHARMACOLOGY & PHARMACY Toxicology Pub Date : 2024-05-25 DOI:10.1016/j.tox.2024.153844
Yiren Xiong , Guoqiang Guo , Hongyi Xian , Zuqing Hu , Di Ouyang , Jiayi He , Shanshan He , Renyi Liu , Zhenjie Gao , Meilin Tang , Ying Chen , Suqin Tan , Xiaoqi Zhu , Abudumijiti Abulimiti , Sujin Zheng , Hehai Huang , Dalin Hu
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引用次数: 0

摘要

三丁基氯化锡(TBTC)是一种无处不在的环境污染物,对人类健康有各种不利影响。外泌体是细胞衍生的信号和物质运输囊泡。这项研究旨在探讨外泌体是否能通过其转运功能影响 TBTC 的毒性效应。采用 CCK-8、流式细胞术、彗星试验和微核试验分别分析了 TBTC 对 MCF-7 细胞造成的细胞毒性、DNA 和染色体损伤。采用超速离心、透射电子显微镜(TEM)和双喹啉酸(BCA)方法对外泌体进行了表征和定量分析。液相色谱-质谱法(LC-MS)检测了外泌体中的 TBTC 含量。分析了外泌体分泌对 TBTC 毒性效应的影响。我们的数据表明,TBTC 对 MCF-7 细胞造成了明显的细胞毒性、DNA 和染色体损伤效应,并显著增加了外泌体分泌。重要的是,TBTC 可通过外泌体被转运出 MCF-7 细胞。此外,当使用 GW4869 阻断外泌体分泌时,TBTC 的毒性效应明显加剧。我们的结论是,TBTC 促进了外泌体的分泌,而外泌体的分泌又将 TBTC 从源细胞中运出,从而减轻了 TBTC 的毒性效应。这项研究为了解外泌体在 TBTC 压力下的作用和机制提供了新的视角。
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MCF-7 cell - derived exosomes were involved in protecting source cells from the damage caused by tributyltin chloride via transport function

Tributyltin chloride (TBTC) is a ubiquitous environmental pollutant with various adverse effects on human health. Exosomes are cell - derived signaling and substance transport vesicles. This investigation aimed to explore whether exosomes could impact the toxic effects caused by TBTC via their transport function. Cytotoxicity, DNA and chromosome damage caused by TBTC on MCF-7 cells were analyzed with CCK-8, flow cytometry, comet assay and micronucleus tests, respectively. Exosomal characterization and quantitative analysis were performed with ultracentrifugation, transmission electron microscope (TEM) and bicinchoninic acid (BCA) methods. TBTC content in exosomes was detected with Liquid Chromatography-Mass Spectrometry (LC-MS). The impacts of exosomal secretion on the toxic effects of TBTC were analyzed. Our data indicated that TBTC caused significant cytotoxicity, DNA and chromosome damage effects on MCF-7 cells, and a significantly increased exosomal secretion. Importantly, TBTC could be transported out of MCF-7 cells by exosomes. Further, when exosomal secretion was blocked with GW4869, the toxic effects of TBTC were significantly exacerbated. We concluded that TBTC promoted exosomal secretion, which in turn transported TBTC out of the source cells to alleviate its toxic effects. This investigation provided a novel insight into the role and mechanism of exosomal release under TBTC stress.

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来源期刊
Toxicology
Toxicology 医学-毒理学
CiteScore
7.80
自引率
4.40%
发文量
222
审稿时长
23 days
期刊介绍: Toxicology is an international, peer-reviewed journal that publishes only the highest quality original scientific research and critical reviews describing hypothesis-based investigations into mechanisms of toxicity associated with exposures to xenobiotic chemicals, particularly as it relates to human health. In this respect "mechanisms" is defined on both the macro (e.g. physiological, biological, kinetic, species, sex, etc.) and molecular (genomic, transcriptomic, metabolic, etc.) scale. Emphasis is placed on findings that identify novel hazards and that can be extrapolated to exposures and mechanisms that are relevant to estimating human risk. Toxicology also publishes brief communications, personal commentaries and opinion articles, as well as concise expert reviews on contemporary topics. All research and review articles published in Toxicology are subject to rigorous peer review. Authors are asked to contact the Editor-in-Chief prior to submitting review articles or commentaries for consideration for publication in Toxicology.
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