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Dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, Danio rerio
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 un...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619386/ https://www.ncbi.nlm.nih.gov/pubmed/26499117 http://dx.doi.org/10.1186/s12864-015-1941-2 |
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author | Bui-Nguyen, Tri M. Baer, Christine E. Lewis, John A. Yang, Dongren Lein, Pamela J. Jackson, David A. |
author_facet | Bui-Nguyen, Tri M. Baer, Christine E. Lewis, John A. Yang, Dongren Lein, Pamela J. Jackson, David A. |
author_sort | Bui-Nguyen, Tri M. |
collection | PubMed |
description | 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 an 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1941-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4619386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46193862015-10-26 Dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, Danio rerio Bui-Nguyen, Tri M. Baer, Christine E. Lewis, John A. Yang, Dongren Lein, Pamela J. Jackson, David A. BMC Genomics Research Article 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 an 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1941-2) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-24 /pmc/articles/PMC4619386/ /pubmed/26499117 http://dx.doi.org/10.1186/s12864-015-1941-2 Text en © Bui-Nguyen et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Bui-Nguyen, Tri M. Baer, Christine E. Lewis, John A. Yang, Dongren Lein, Pamela J. Jackson, David A. Dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, Danio rerio |
title | Dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, Danio rerio |
title_full | Dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, Danio rerio |
title_fullStr | Dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, Danio rerio |
title_full_unstemmed | Dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, Danio rerio |
title_short | Dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, Danio rerio |
title_sort | dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, danio rerio |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619386/ https://www.ncbi.nlm.nih.gov/pubmed/26499117 http://dx.doi.org/10.1186/s12864-015-1941-2 |
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