PUBLICATION
Whole adult organism transcriptional profiling of acute metal exposures in male zebrafish
- Authors
- Hussainzada, N., Lewis, J.A., Baer, C.E., Ippolito, D.L., Jackson, D.A., Stallings, J.D.
- ID
- ZDB-PUB-140513-383
- Date
- 2014
- Source
- BMC pharmacology & toxicology 15: 15 (Journal)
- Registered Authors
- Keywords
- none
- Datasets
- GEO:GSE50648
- MeSH Terms
-
- Animals
- Behavior, Animal/drug effects
- Chromates/toxicity*
- Cobalt/toxicity*
- Fish Proteins/genetics
- Gene Expression Profiling
- Gene Expression Regulation/drug effects*
- Gills/drug effects
- Gills/pathology
- Intestines/drug effects
- Intestines/pathology
- Male
- Nickel/toxicity*
- Olfactory Mucosa/drug effects
- Olfactory Mucosa/pathology
- Oligonucleotide Array Sequence Analysis
- Pharynx/drug effects
- Pharynx/pathology
- Water Pollutants, Chemical/toxicity*
- Zebrafish/genetics
- Zebrafish/physiology
- PubMed
- 24612858 Full text @ BMC Pharmacol Toxicol
- CTD
- 24612858
Citation
Hussainzada, N., Lewis, J.A., Baer, C.E., Ippolito, D.L., Jackson, D.A., Stallings, J.D. (2014) Whole adult organism transcriptional profiling of acute metal exposures in male zebrafish. BMC pharmacology & toxicology. 15:15.
Abstract
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 LC20, LC40 and LC60. 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping