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| Status |
Public on Nov 05, 2015 |
| Title |
Dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, Danio rerio |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by array
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| Summary |
Background: Exposure to dichlorvos (DDVP), an organophosphorus pesticide, is known to result in neurotoxicity as well as other metabolic perturbations. However, the molecular causes of DDVP toxicity are poorly understood, especially in cells other than neurons and muscle cells. To obtain a better understanding of the process of non-neuronal DDVP toxicity, we exposed zebrafish to different concentrations of DDVP, and investigated the resulting changes in liver histology and gene transcription. Results: Functional enrichment analysis of genes affected by DDVP exposure identified a number of processes involved in energy utilization and stress response in the liver. The abundance of transcripts for proteins involved in glucose metabolism was profoundly affected, suggesting that carbon flux might be diverted toward the pentose phosphate pathway to compensate for elevated demand for energy and reducing equivalents for detoxification. Strikingly, many transcripts for molecules involved in β-oxidation and fatty acid synthesis were down-regulated. We found increases in message levels for molecules involved in reactive oxygen species responses as well as ubiquitination, proteasomal degradation, and autophagy. To ensure that the effects of DDVP on energy metabolism were not simply a consequence of poor feeding because of neuromuscular impairment, we fasted fish for 29 or 50 h and analyzed liver gene expression in them. The patterns of gene expression for energy metabolism in fasted and DDVP-exposed fish were markedly different. Conclusion: We observed coordinated changes in the expression of a large number of genes involved in energy metabolism and responses to oxidative stress. These results argue that an appreciable part of the effect of DDVP is on energy metabolism and is regulated at the message level. Although we observed some evidence of neuromuscular impairment in exposed fish that may have resulted in reduced feeding, the alterations in gene expression in exposed fish cannot readily be explained by nutrient deprivation.
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| Overall design |
Dichlorvos induced changes in gene expression in zebrafish were measured after 24 h exposures. A total of 20 arrays were processed with 4 replicates for each exposure condition (low, mid, and high) and 4 replicates for each of 2 control sets. Also, fasting induced changes in gene expression in zebrafish were measured after 24 hours fasting and 50 hours fasting. A total of 12 arrays were processed with 4 replicates for each exposure condition (no fasting, 24h fasting, 50h fasting).
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| Contributor(s) |
Bui-Nguyen TM, Baer CE, Lewis JA, Yang D, Lein PJ, Jackson DA |
| Citation(s) |
26499117 |
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| Submission date |
Feb 24, 2015 |
| Last update date |
Nov 07, 2015 |
| Contact name |
Christine Baer |
| E-mail(s) |
[email protected]
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| Organization name |
Excet, Inc. / USACEHR
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| Department |
Environmental Health Program
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| Street address |
568 Doughten Drive
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| City |
Ft. Detrick |
| State/province |
MD |
| ZIP/Postal code |
21702-5010 |
| Country |
USA |
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| Platforms (1) |
| GPL7301 |
Agilent-019161 D. rerio (Zebrafish) Oligo Microarray (V2) G2519F (Probe Name version) |
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| Samples (32)
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| Relations |
| BioProject |
PRJNA276272 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE66257_RAW.tar |
166.5 Mb |
(http)(custom) |
TAR (of GPR, TXT) |
| Processed data included within Sample table |
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