{"title":"Extracellular vesicles-derived long noncoding RNAs participated in benzene hematotoxicity by mediating apoptosis and autophagy","authors":"","doi":"10.1016/j.taap.2024.117076","DOIUrl":null,"url":null,"abstract":"<div><p>Benzene is a common contaminant in the workplace and wider environment, which induces hematotoxicity. Our previous study has implicated that lncRNAs mediated apoptosis and autophagy induced by benzene. Nevertheless, the roles of extracellular vesicle(EVs)-derived lncRNAs in benzene toxicity are unknown. However, the role of EVs and EVs-derived lncRNAs in benzene-induced toxicity remains unclear. In this research, we explored the function of EVs and EVs-derived lncRNAs in cell-cell communication through benzene-induced apoptosis and autophagy. Our findings demonstrated that EVs derived from 1,4-BQ-treated cells treated cells and coculture with 1,4-BQ-treated cells enhanced apoptosis and autophagy via regulating the pathways of PI3K-AKT-mTOR and chaperone-mediated autophagy. Treating with GW4869 in 1,4-BQ-treated cells significantly inhibited EV secretion, which reduced apoptosis and autophagy. Furthermore, we identified a set of differentially expressed autophagy- and apoptosis-related lncRNAs using EVs-derived lncRNA sequencing. Among them, 8 candidate lncRNAs were upregulated in EVs derived from 1,4-BQ-treated cells, as determined by lncRNA sequencing and qRT–PCR. Importantly, these lncRNAs were also increased in the serum EVs of benzene-exposed workers. 1,4-BQ-treated cells released EVs that transfer differentially expressed lncRNAs, thereby inducing apoptosis and autophagy in the recipient cells. The above results support the hypothesis that EVs-derived lncRNAs participate in intercellular communication during benzene-induced hematotoxicity and function as potential biomarkers for risk assessment of benzene-exposed workers.</p></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology and applied pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0041008X24002746","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Benzene is a common contaminant in the workplace and wider environment, which induces hematotoxicity. Our previous study has implicated that lncRNAs mediated apoptosis and autophagy induced by benzene. Nevertheless, the roles of extracellular vesicle(EVs)-derived lncRNAs in benzene toxicity are unknown. However, the role of EVs and EVs-derived lncRNAs in benzene-induced toxicity remains unclear. In this research, we explored the function of EVs and EVs-derived lncRNAs in cell-cell communication through benzene-induced apoptosis and autophagy. Our findings demonstrated that EVs derived from 1,4-BQ-treated cells treated cells and coculture with 1,4-BQ-treated cells enhanced apoptosis and autophagy via regulating the pathways of PI3K-AKT-mTOR and chaperone-mediated autophagy. Treating with GW4869 in 1,4-BQ-treated cells significantly inhibited EV secretion, which reduced apoptosis and autophagy. Furthermore, we identified a set of differentially expressed autophagy- and apoptosis-related lncRNAs using EVs-derived lncRNA sequencing. Among them, 8 candidate lncRNAs were upregulated in EVs derived from 1,4-BQ-treated cells, as determined by lncRNA sequencing and qRT–PCR. Importantly, these lncRNAs were also increased in the serum EVs of benzene-exposed workers. 1,4-BQ-treated cells released EVs that transfer differentially expressed lncRNAs, thereby inducing apoptosis and autophagy in the recipient cells. The above results support the hypothesis that EVs-derived lncRNAs participate in intercellular communication during benzene-induced hematotoxicity and function as potential biomarkers for risk assessment of benzene-exposed workers.
期刊介绍:
Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products.
Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged.
Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.