PUBLICATION
Microcystin-LR-regulated transcriptome dynamics in ZFL cells
- Authors
- Lu, X., Tian, J., Wen, H., Jiang, M., Liu, W., Wu, F., Yu, L., Zhong, S.
- ID
- ZDB-PUB-190529-10
- Date
- 2019
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 212: 222-232 (Journal)
- Registered Authors
- Keywords
- Gene transcription, Microcystin, Signaling pathway, Transcriptome, ZFL cell line
- MeSH Terms
-
- Animals
- Cell Line
- Down-Regulation/drug effects
- Hepatocytes/drug effects
- Humans
- Inhibitory Concentration 50
- Liver/cytology
- Liver/drug effects
- Microcystins/toxicity*
- Mitogen-Activated Protein Kinases/metabolism
- Signal Transduction/drug effects*
- Transcriptome/drug effects*
- Water Pollutants, Chemical/toxicity
- Zebrafish/physiology
- PubMed
- 31136897 Full text @ Aquat. Toxicol.
Citation
Lu, X., Tian, J., Wen, H., Jiang, M., Liu, W., Wu, F., Yu, L., Zhong, S. (2019) Microcystin-LR-regulated transcriptome dynamics in ZFL cells. Aquatic toxicology (Amsterdam, Netherlands). 212:222-232.
Abstract
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 μg/mL. The ZFL cells were exposed to 10 μg/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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping