Triclosan induces pyroptosis by activation of the caspase-9/3/gasdermin E axis

IF 5.3 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Emerging Contaminants Pub Date : 2024-10-20 DOI:10.1016/j.emcon.2024.100425
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Abstract

The high concentrations of TCS in personal care products, and the potential for even greater exposure in occupational settings, raise significant concerns about its cytotoxic effects. Numorous studies highlight the importance of understanding the molecular mechanisms of pyroptosis in toxicological research on environmental pollutants. However, it remains unclear whether TCS exposure could induce GSDME-mediated pyroptosis. In this study, we aimed to investigate the cytotoxic effects of 200 μM TCS on L02 cells and elucidate the molecular mechanisms involved in TCS-induced pyroptosis, a novel form of cell death. Our results demonstrate that TCS inhibits the proliferation of L02 cells in a dose-dependent manner and triggers caspase-dependent cell death, leading to mitochondrial dysfunction and subsequent pyroptosis through the activation of the caspase-9/3/GSDME axis. Furthermore, through transcriptional and metabolomic analyses, we identified alterations in the PI3K-Akt and MAPK cellular signaling pathways, as well as changes in carbon and nitrogen metabolism. Our data provide valuable insights into the biotoxicity of high TCS concentrations and establish a theoretical basis for future studies on its impact and risk.

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三氯生通过激活 Caspase-9/3/gasdermin E 轴诱导脓毒症
个人护理产品中三氯杀螨醇的浓度很高,在职业环境中的接触量可能更大,这引起了人们对其细胞毒性效应的极大关注。大量研究表明,在环境污染物的毒理学研究中,了解热变态反应的分子机制非常重要。然而,三氯氢硅暴露是否会诱导 GSDME 介导的热蛋白沉积,目前仍不清楚。在本研究中,我们旨在研究 200 μM TCS 对 L02 细胞的细胞毒性作用,并阐明 TCS 诱导的新细胞死亡形式--热蜕变的分子机制。我们的研究结果表明,TCS 以剂量依赖性方式抑制 L02 细胞的增殖,并通过激活 caspase-9/3/GSDME 轴引发依赖于 caspase 的细胞死亡,导致线粒体功能障碍和随后的热凋亡。此外,通过转录和代谢组学分析,我们发现了 PI3K-Akt 和 MAPK 细胞信号通路的改变,以及碳和氮代谢的变化。我们的数据为了解高浓度三氯氢硅的生物毒性提供了宝贵的见解,并为今后研究其影响和风险奠定了理论基础。
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来源期刊
Emerging Contaminants
Emerging Contaminants Medicine-Public Health, Environmental and Occupational Health
CiteScore
10.00
自引率
6.70%
发文量
35
审稿时长
44 days
期刊介绍: Emerging Contaminants is an outlet for world-leading research addressing problems associated with environmental contamination caused by emerging contaminants and their solutions. Emerging contaminants are defined as chemicals that are not currently (or have been only recently) regulated and about which there exist concerns regarding their impact on human or ecological health. Examples of emerging contaminants include disinfection by-products, pharmaceutical and personal care products, persistent organic chemicals, and mercury etc. as well as their degradation products. We encourage papers addressing science that facilitates greater understanding of the nature, extent, and impacts of the presence of emerging contaminants in the environment; technology that exploits original principles to reduce and control their environmental presence; as well as the development, implementation and efficacy of national and international policies to protect human health and the environment from emerging contaminants.
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