磷酸三苯酯经miRNA介导的人肝细胞脂类代谢干扰作用
TPhP Induced Lipid Metabolism Disruption Mediated by miRNA in Hepatocyte
查看参考文献35篇
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文摘
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磷酸三苯酯(triphenyl phosphate, TPhP)是近年来广泛应用于电子产品的磷系阻燃剂,其脂类代谢干扰作用受到广泛关注,而microRNAs(miRNAs)在TPhP脂类代谢干扰过程中的调控作用仍鲜有报道。本研究通过探讨TPhP暴露条件下人肝细胞的细胞活性、TPhP清除速率与miRNAs表达调控特征,并与已获得转录组数据联合分析,明确TPhP经miRNA介导的脂类代谢干扰作用。在不同浓度TPhP暴露处理48 h后,人肝细胞的细胞活性随着暴露浓度呈先上升后下降的趋势,半数致死效应剂量为46.7 μmol·L~(-1) 。在5 μg·mL~(-1)的TPhP暴露3 h和48 h后,TPhP的清除率分别为73.9%和85.1% 。人肝细胞多个miRNAs表达差异显著,差异表达miRNAs所调控的靶基因主要参与代谢、脂肪酸合成、类固醇合成及癌症相关通路。通过转录组关联分析,差异表达miR-34c-5p、miR-301a-5p和miR-7等多个miRNAs对脂类代谢相关通路的关键基因具有调控作用,并构成miRNA-mRNA调控网络。综上所述,人肝细胞对TPhP具有较高的清除效率,TPhP暴露诱导miRNA差异表达所介导的脂类代谢干扰作用是TPhP对人肝细胞的主要毒性作用,miR-7和miR-4484等miRNAs能作为TPhP胁迫下脂类代谢干扰作用的潜在生物指示物。 |
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其他语种文摘
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Triphenyl phosphate (TPhP) is one of the novel alternative retardants with increasing utility. As a potential obesogen, the direct disruption of TPhP on lipid metabolism in hepatocyte has been widely studied. However, the microRNAs (miRNAs) regulation patterns of lipid metabolism disruption effects in hepatocyte under TPhP exposure remain unknown. This study aimed to elucidate the adverse effect of TPhP on hepatocyte through cell viability, TPhP clearance, and epigenetic miRNA alterations of hepatocytes at short (3 h) and long term (48 h) exposures to TPhP. The cell viability of hepatocyte raised at the low TPhP concentration treatments but dramatically decreased after the 10 μg·mL~(-1) TPhP treatment, and concentration for 50% of maximal inhibitory effect was 46.7 μmol·L~(-1). The clearance rates of TPhP in hepatocyte were 73.9% and 85.1% after 3 h and 48 h incubations, respectively. Plenty of miRNAs were differentially expressed under TPhP treatments of 5 μg·mL~(-1). The predicted target genes of these differential expressed miRNAs were mainly involved in metabolic, fatty acid biosynthesis, steroid biosynthesis and cancer related pathways. The regulation network of miRNA-mRNA was constructed according to the correlations between miR-34c-5p, miR-301a-5p, and miR-7 and lipid metabolism related genes. Lipid metabolism disruption by TPhP was achieved by a proposed integration network of differential expressed mRNAs and miRNAs. Our study provides important insight in potential miRNAs biomarkers such as miR-4484 and miR-7 and the miRNA-mediated lipid metabolism disruption effect on human hepatocytes under TPhP treatment. |
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来源
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生态毒理学报
,2021,16(2):140-150 【核心库】
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DOI
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10.7524/AJE.1673-5897.20200306001
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关键词
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磷酸三苯酯
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人肝细胞
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脂类代谢干扰
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miRNAs
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地址
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中山大学农学院, 深圳, 518107
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生态环境部华南环境科学研究所, 国家环境保护环境污染健康风险评价重点实验室, 广州, 510530
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湖南工学院安全与环境工程学院, 衡阳, 421002
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中国科学院广州地球化学研究所, 有机地球化学国家重点实验室, 广州, 510640
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语种
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中文 |
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文献类型
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研究性论文 |
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ISSN
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1673-5897 |
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学科
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环境科学基础理论 |
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基金
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国家自然科学基金青年基金资助项目
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广东省广州市科技计划项目
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国家自然科学基金重点项目
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文献收藏号
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CSCD:7020306
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参考文献 共
35
共2页
|
|
1.
He C T. Occurrence of organophosphorus flame retardants in indoor dust in multiple microenvironments of Southern China and implications for human exposure.
Chemosphere,2015,133:47-52
|
被引
20
次
|
|
|
|
|
2.
Tajima S. Detection and intake assessment of organophosphate flame retardants in house dust in Japanese dwellings.
Science of the Total Environment,2014,478:190-199
|
被引
10
次
|
|
|
|
|
3.
Qiao L. Analysis of human hair to assess exposure to organophosphate flame retardants: Influence of hair segments and gender differences.
Environmental Research,2016,148:177-183
|
被引
6
次
|
|
|
|
|
4.
彭涛. 磷酸三苯酯对斑马鱼早期生命阶段的神经毒性研究.
生态毒理学报,2016,11(1):254-260
|
被引
10
次
|
|
|
|
|
5.
张杏丽. 基于代谢组学技术分析磷酸三苯酯诱导斑马鱼胚胎发育毒性的分子机制.
生态毒理学报,2019,14(3):79-89
|
被引
4
次
|
|
|
|
|
6.
Pillai H K. Ligand binding and activation of PPARγ by Firemaster® 550: Effects on adipogenesis and osteogenesis in vitro.
Environmental Health Perspectives,2014,122(11):1225-1232
|
被引
5
次
|
|
|
|
|
7.
Tung E W Y. Adipogenic effects and gene expression profiling of firemaster® 550 components in human primary preadipocytes.
Environmental Health Perspectives,2017,125(9):097013
|
被引
2
次
|
|
|
|
|
8.
Bleck B. MicroRNA-375 regulation of thymic stromal lymphopoietin by diesel exhaust particles and ambient particulate matter in human bronchial epithelial cells.
Journal of Immunology,2013,190(7):3757-3763
|
被引
5
次
|
|
|
|
|
9.
Fossati S. Ambient particulate air pollution and microRNAs in elderly men.
Epidemiology,2014,25(1):68-78
|
被引
5
次
|
|
|
|
|
10.
Stanitz E. Evaluation of microRNA expression pattern of gastric adenocarcinoma associated with socioeconomic, environmental and lifestyle factors in northwestern Hungary.
Anticancer Research,2013,33(8):3195-3200
|
被引
4
次
|
|
|
|
|
11.
Wang F. Prenatal and neonatal exposure to perfluorooctane sulfonic acid results in aberrant changes in miRNA expression profile and levels in developing rat livers.
Environmental Toxicology,2015,30(6):712-723
|
被引
3
次
|
|
|
|
|
12.
Singh N P. Prenatal exposure to TCDD triggers significant modulation of microRNA expression profile in the thymus that affects consequent gene expression.
PLoS One,2012,7(9):e45054
|
被引
1
次
|
|
|
|
|
13.
Vrijens K. MicroRNAs as potential signatures of environmental exposure or effect: A systematic review.
Environmental Health Perspectives,2015,123(5):399-411
|
被引
6
次
|
|
|
|
|
14.
Su G Y. Rapid in vitro metabolism of the flame retardant triphenyl phosphate and effects on cytotoxicity and mRNA expression in chicken embryonic hepatocytes.
Environmental Science & Technology,2014,48(22):13511-13519
|
被引
7
次
|
|
|
|
|
15.
Betel D. The microRNA.org resource: Targets and expression.
Nucleic Acids Research,2008,36:D149-D153
|
被引
62
次
|
|
|
|
|
16.
Agarwal V. Predicting effective microRNA target sites in mammalian mRNAs.
eLIFE,2015,4:05005
|
被引
106
次
|
|
|
|
|
17.
何春桃.
广东省典型住区室内灰尘常见有机阻燃剂污染特征及毒性,2016:67-95
|
被引
1
次
|
|
|
|
|
18.
Belcher S M. In vitro assessment of human nuclear hormone receptor activity and cytotoxicity of the flame retardant mixture FM 550 and its triarylphosphate and brominated components.
Toxicology Letters,2014,228(2):93-102
|
被引
3
次
|
|
|
|
|
19.
van den Eede N. First insights in the metabolism of phosphate flame retardants and plasticizers using human liver fractions.
Toxicology Letters,2013,223(1):9-15
|
被引
17
次
|
|
|
|
|
20.
Du Z K. TPhP exposure disturbs carbohydrate metabolism, lipid metabolism, and the DNA damage repair system in zebrafish liver.
Scientific Reports,2016,6:21827
|
被引
6
次
|
|
|
|
|
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