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Microcystin-LR-regulated transcriptome dynamics in ZFL cells

文献类型： 外文期刊

作者： Lu, Xing 1 ; Tian, Juan 1 ; Wen, Hua 1 ; Jiang, Ming 1 ; Liu, Wei 1 ; Wu, Fan 1 ; Yu, Lijuan 1 ; Zhong, Shan 2 ;

作者机构： 1.Chinese Acad Fishery Sci, Yangtze River Fisheries Res Inst, Minist Agr, Key Lab Freshwater Biodivers Conservat & Utilizat, Wuhan 430223, Hubei, Peoples R China

2.Wuhan Univ, Dept Genet, Wuhan 430071, Hubei, Peoples R China

3.Hubei Prov Key Lab Dev Originated Dis, Wuhan 430071, Hubei, Peoples R China

4.Hubei Prov Key Lab Allergy & Immunol, Wuhan 430071, Hubei, Peoples R China

关键词： Microcystin; ZFL cell line; Transcriptome; Gene transcription; Signaling pathway

期刊名称：AQUATIC TOXICOLOGY （ 影响因子：4.964； 五年影响因子：5.071 ）

ISSN： 0166-445X

年卷期： 2019 年 212 卷

页码：

收录情况： SCI

摘要： Microcystin-LR (MC-LR) is a highly toxic hepatotoxin that poses great hazards to aquatic organisms and even human health. The zebrafish liver cell line (ZFL) is a valuable model for investigating toxicity and metabolism of toxicants. However, the toxicity of MC-LR and its effects on gene transcription of ZFL cells remains to be characterized. In this study, we determined the toxicity of MC-LR for ZFL cells and investigated the effects of MC-LR on cellular transcriptome dynamics. The EC50 of MC-LR for ZFL cells was 80.123 mu g/mL. The ZFL cells were exposed to 10 mu g/mL MC-LR for 0, 1, 3, 6, 12 or 24 h, and RNA-sequencing was performed to analyze gene transcription. A total of 10,209 genes were found to be regulated by MC-LR. The numbers of up- and down-regulated genes at different time points ranged from 2179 to 3202 and from 1501 to 2597, respectively. Furthermore, 1543 genes underwent differential splicing (AS) upon MC-LR exposure, of which 620 were not identified as differentially expressed gene (DEG). The effects of MC-LR on cellular functions were highly time-dependent. MAPK (mitogen-activated protein kinase) and FoxO (forkhead box O) signaling pathways were the most prominent pathways activated by MC-LR. Steroid biosynthesis and terpenoid backbone biosynthesis were the most enriched for the down-regulated genes. A gene regulatory network was constructed from the expression profile datasets and the candidate master transcription factors were identified. Our results shed light on the molecular mechanisms of MC-LR cellular toxicity and the transcriptome landscapes of ZFL cells upon MC-LR toxicity.

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