{"title":"Triclosan induces pyroptosis by activation of the caspase-9/3/gasdermin E axis","authors":"","doi":"10.1016/j.emcon.2024.100425","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":11539,"journal":{"name":"Emerging Contaminants","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Emerging Contaminants","FirstCategoryId":"1087","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2405665024001264","RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
引用次数: 0
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.
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.