PUBLICATION
Molecular targets of TBBPA in zebrafish analysed through integration of genomic and proteomic approaches
- Authors
- De Wit, M., Keil, D., Remmerie, N., Ven, K.V., Brandhof, E.J., Knapen, D., Witters, E., and Coen, W.D.
- ID
- ZDB-PUB-081105-7
- Date
- 2008
- Source
- Chemosphere 74(1): 96-105 (Journal)
- Registered Authors
- Knapen, Dries
- Keywords
- Genomics, Proteomics, Zebrafish, Brominated flame retardants
- MeSH Terms
-
- Animals
- Electrophoresis, Gel, Two-Dimensional
- Flame Retardants/toxicity
- Gene Expression Regulation/drug effects
- Genomics/methods*
- Oligonucleotide Array Sequence Analysis
- Polybrominated Biphenyls/toxicity*
- Proteomics/methods*
- Zebrafish/genetics*
- Zebrafish/metabolism*
- PubMed
- 18976794 Full text @ Chemosphere
- CTD
- 18976794
Citation
De Wit, M., Keil, D., Remmerie, N., Ven, K.V., Brandhof, E.J., Knapen, D., Witters, E., and Coen, W.D. (2008) Molecular targets of TBBPA in zebrafish analysed through integration of genomic and proteomic approaches. Chemosphere. 74(1):96-105.
Abstract
Tetrabromobisphenol-A (TBBPA) is nowadays one of the most frequently used brominated flame retardants (BFRs) and can be considered as a high production volume chemical. Over the last decade, numerous reports of increasing concentrations of BFRs in the environment and humans have been published. However, the toxicological knowledge on TBBPA, and more specifically its molecular mode of action, is rather fragmentary. In this study two populations of adult zebrafish (Danio rerio) were exposed for 14 days to 0.75muM and 1.5muM TBBPA. Subsequently, we employed a combined transcriptomic and proteomic approach to evaluate the molecular effects of TBBPA in zebrafish liver. Oligonucleotide microarrays were used to study the effects on gene expression levels. These results were validated through real-time PCR. The proteome of the liver was analysed by means of differential in-gel electrophoresis (DiGE), an innovative application of traditional 2D-PAGE. Combination of the extracted datasets allowed reassembling of individual molecular responses into a comprehensive overview of affected molecular pathways. Interpretation of the results depicted an interference of thyroid and Vitamin A homeostasis in the exposed zebrafish, TBBPA also elicited responses indicating onset of oxidative stress and general stress responses. Additionally, numerous differentially expressed transcripts could be associated with defence mechanisms or corresponded to metabolizing enzymes. Furthermore, cellular metabolism was clearly affected, illustrated as disturbance of e.g. lipid, carbohydrate, and organic acid metabolic processes. Summarizing, these results enabled us to hypothesize several working mechanisms of TBBPA and demonstrated the potential of a combined genome and proteome approach to generate detailed mechanistic toxicological information.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping