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Whole adult organism transcriptional profiling of acute metal exposures in male Zebrafish

BACKGROUND: A convergence of technological breakthroughs in the past decade has facilitated the development of rapid screening tools for biomarkers of toxicant exposure and effect. Platforms using the whole adult organism to evaluate the genome-wide response to toxicants are especially attractive. R...

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Autores principales: Hussainzada, Naissan, Lewis, John A, Baer, Christine E, Ippolito, Danielle L, Jackson, David A, Stallings, Jonathan D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007779/
https://www.ncbi.nlm.nih.gov/pubmed/24612858
http://dx.doi.org/10.1186/2050-6511-15-15
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author Hussainzada, Naissan
Lewis, John A
Baer, Christine E
Ippolito, Danielle L
Jackson, David A
Stallings, Jonathan D
author_facet Hussainzada, Naissan
Lewis, John A
Baer, Christine E
Ippolito, Danielle L
Jackson, David A
Stallings, Jonathan D
author_sort Hussainzada, Naissan
collection PubMed
description BACKGROUND: A convergence of technological breakthroughs in the past decade has facilitated the development of rapid screening tools for biomarkers of toxicant exposure and effect. Platforms using the whole adult organism to evaluate the genome-wide response to toxicants are especially attractive. Recent work demonstrates the feasibility of this approach in vertebrates using the experimentally robust zebrafish model. In the present study, we evaluated gene expression changes in whole adult male zebrafish following an acute 24 hr high dose exposure to three metals with known human health risks. Male adult zebrafish were exposed to nickel chloride, cobalt chloride or sodium dichromate concentrations corresponding to their respective 96 hr LC(20), LC(40) and LC(60). Histopathology was performed on a subset of metal-exposed zebrafish to phenotypically anchor transcriptional changes associated with each metal. RESULTS: Comparative analysis identified subsets of differentially expressed transcripts both overlapping and unique to each metal. Application of gene ontology (GO) and transcription factor (TF) enrichment algorithms revealed a number of key biological processes perturbed by metal poisonings and the master transcriptional regulators mediating gene expression changes. Metal poisoning differentially activated biological processes associated with ribosome biogenesis, proteosomal degradation, and p53 signaling cascades, while repressing oxygen-generating pathways associated with amino acid and lipid metabolism. Despite appreciable effects on gene regulation, nickel poisoning did not induce any morphological alterations in male zebrafish organs and tissues. Histopathological effects of cobalt remained confined to the olfactory system, while chromium targeted the gills, pharynx, and intestinal mucosa. A number of enriched transcription factors mediated the observed gene response to metal poisoning, including known targets such as p53, HIF1α, and the myc oncogene, and novel regulatory factors such as XBP1, GATA6 and HNF3β. CONCLUSIONS: This work uses an experimentally innovative approach to capture global responses to metal poisoning and provides mechanistic insights into metal toxicity.
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spelling pubmed-40077792014-05-03 Whole adult organism transcriptional profiling of acute metal exposures in male Zebrafish Hussainzada, Naissan Lewis, John A Baer, Christine E Ippolito, Danielle L Jackson, David A Stallings, Jonathan D BMC Pharmacol Toxicol Research Article BACKGROUND: A convergence of technological breakthroughs in the past decade has facilitated the development of rapid screening tools for biomarkers of toxicant exposure and effect. Platforms using the whole adult organism to evaluate the genome-wide response to toxicants are especially attractive. Recent work demonstrates the feasibility of this approach in vertebrates using the experimentally robust zebrafish model. In the present study, we evaluated gene expression changes in whole adult male zebrafish following an acute 24 hr high dose exposure to three metals with known human health risks. Male adult zebrafish were exposed to nickel chloride, cobalt chloride or sodium dichromate concentrations corresponding to their respective 96 hr LC(20), LC(40) and LC(60). Histopathology was performed on a subset of metal-exposed zebrafish to phenotypically anchor transcriptional changes associated with each metal. RESULTS: Comparative analysis identified subsets of differentially expressed transcripts both overlapping and unique to each metal. Application of gene ontology (GO) and transcription factor (TF) enrichment algorithms revealed a number of key biological processes perturbed by metal poisonings and the master transcriptional regulators mediating gene expression changes. Metal poisoning differentially activated biological processes associated with ribosome biogenesis, proteosomal degradation, and p53 signaling cascades, while repressing oxygen-generating pathways associated with amino acid and lipid metabolism. Despite appreciable effects on gene regulation, nickel poisoning did not induce any morphological alterations in male zebrafish organs and tissues. Histopathological effects of cobalt remained confined to the olfactory system, while chromium targeted the gills, pharynx, and intestinal mucosa. A number of enriched transcription factors mediated the observed gene response to metal poisoning, including known targets such as p53, HIF1α, and the myc oncogene, and novel regulatory factors such as XBP1, GATA6 and HNF3β. CONCLUSIONS: This work uses an experimentally innovative approach to capture global responses to metal poisoning and provides mechanistic insights into metal toxicity. BioMed Central 2014-03-10 /pmc/articles/PMC4007779/ /pubmed/24612858 http://dx.doi.org/10.1186/2050-6511-15-15 Text en Copyright © 2014 Hussainzada et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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
Hussainzada, Naissan
Lewis, John A
Baer, Christine E
Ippolito, Danielle L
Jackson, David A
Stallings, Jonathan D
Whole adult organism transcriptional profiling of acute metal exposures in male Zebrafish
title Whole adult organism transcriptional profiling of acute metal exposures in male Zebrafish
title_full Whole adult organism transcriptional profiling of acute metal exposures in male Zebrafish
title_fullStr Whole adult organism transcriptional profiling of acute metal exposures in male Zebrafish
title_full_unstemmed Whole adult organism transcriptional profiling of acute metal exposures in male Zebrafish
title_short Whole adult organism transcriptional profiling of acute metal exposures in male Zebrafish
title_sort whole adult organism transcriptional profiling of acute metal exposures in male zebrafish
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007779/
https://www.ncbi.nlm.nih.gov/pubmed/24612858
http://dx.doi.org/10.1186/2050-6511-15-15
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