双酚a破坏线粒体功能,导致人羊膜间充质间质细胞衰老和凋亡。

IF 7 2区 生物学 Q1 CELL BIOLOGY
Sara Ficai, Andrea Papait, Marta Magatti, Alice Masserdotti, Michael Gasik, Antonietta Rosa Silini, Ornella Parolini
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引用次数: 0

摘要

在今天的背景下,微塑料污染已成为一个日益紧迫的问题,不仅对环境的影响,而且对人类健康的假定负面影响。现在已经确定,微塑料(直径100毫米)可以通过摄入、吸入、皮肤接触以及母婴传播进入人体。令人担忧的是,最近在人类胎盘中发现了微塑料。在微塑料的降解副产物中,双酚a (BPA)已成为一种危险化学品,具有多系统水平的潜在毒性,特别是在人类发育的早期阶段。在此基础上,我们的研究重点是评估BPA对人足月胎盘羊膜间充质细胞(hAMSC)特性和功能的影响。羊膜包裹着胎儿,对母亲可能遇到的有毒化学物质和污染物起着基本的保护作用。我们的研究揭示了暴露于浓度增加的BPA如何损害hAMSC中的线粒体功能,导致线粒体水平活性氧(mtROS)的产生增加。这反过来又导致p53的稳定,从而引发p21和p27编码基因的表达增加,以及Bax和Bcl-2基因表达的不平衡。此外,我们观察到与衰老相关分泌表型(SASP)相关的细胞因子和趋化因子的表达上调。增加的氧化应激在bpa介导的毒性中起着核心作用,可触发衰老途径的激活,或由于压倒性的应激条件导致细胞死亡。因此,我们的研究结果为BPA的作用机制提供了新的见解,并阐明了其对hAMSC功能的影响。这强调了重新考虑双酚a作为塑料添加剂的使用的迫切需要,以减轻对婴儿的潜在不利影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bisphenol-A disrupts mitochondrial functionality leading to senescence and apoptosis in human amniotic mesenchymal stromal cells.

In today's context, microplastic pollution has become an increasingly pressing issue not only for the environmental fallout but also for the assumed negative effects on human health. It is now well-established that microplastics (>1 mm in size) can enter the human body through ingestion, inhalation, dermal contact and also maternal-fetal transmission. Alarming were the recent findings of microplastics within the human term placenta. Among the degradation by-products of microplastics, Bisphenol-A (BPA) has emerged as a hazardous chemical, with potential toxicity at multisystemic level, particularly on the earliest stages of human development. Based on these findings, our study focuses on assessing the impact of BPA on properties and functions of mesenchymal stromal cells isolated from the amniotic membrane (hAMSC) of the human term placenta. The amniotic membrane surrounds the fetus, playing a fundamental protective role toward toxic chemicals and pollutants that the mother may encounter. Our research revealed how exposure to increasing concentrations of BPA compromise mitochondrial functionality in hAMSC, resulting in enhanced production of reactive oxygen species at mitochondrial level (mtROS). This, in turn, leads to the stabilization of p53, which triggers an increased expression of p21 and p27 encoding genes and an imbalance in the genetic expression of Bax and Bcl-2. Additionally, we observed upregulated expression of cytokines and chemokines associated with the senescence-associated secretory phenotype (SASP). The increased oxidative stress, which plays a central role in BPA-mediated toxicity, can trigger the activation of the senescence pathways, or culminate in cell death, due to the overwhelming stress conditions. Therefore, our results provide novel insights into the mechanism of action of BPA and elucidates its impact on the functionality of hAMSC. This underscores the pressing need to reconsider the use of BPA as a plastic additive, mitigating the potential adverse effects on babies.

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来源期刊
Cell Death Discovery
Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
8.30
自引率
1.40%
发文量
468
审稿时长
9 weeks
期刊介绍: Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
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