PUBLICATION

The Transcriptional Response to Oxidative Stress during Vertebrate Development: Effects of tert-Butylhydroquinone and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin

Authors
Hahn, M.E., McArthur, A.G., Karchner, S.I., Franks, D.G., Jenny, M.J., Timme-Laragy, A.R., Stegeman, J.J., Woodin, B.R., Cipriano, M.J., Linney, E.
ID
ZDB-PUB-141118-3
Date
2014
Source
PLoS One   9: e113158 (Journal)
Registered Authors
Franks, Diana, Hahn, Mark E., Karchner, Sibel, Linney, Elwood, Stegeman, John J.
Keywords
none
Datasets
GEO:GSE10157
MeSH Terms
  • Animals
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/growth & development
  • Antioxidants/toxicity
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism*
  • Embryo, Nonmammalian/pathology
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental/drug effects*
  • Hydroquinones/toxicity*
  • Oxidation-Reduction
  • Oxidative Stress/drug effects*
  • Teratogens/toxicity
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
25402455 Full text @ PLoS One
Abstract
Oxidative stress is an important mechanism of chemical toxicity, contributing to teratogenesis and to cardiovascular and neurodegenerative diseases. Developing animals may be especially sensitive to chemicals causing oxidative stress. The developmental expression and inducibility of anti-oxidant defenses through activation of NF-E2-related factor 2 (NRF2) affect susceptibility to oxidants, but the embryonic response to oxidants is not well understood. To assess the response to chemically mediated oxidative stress and how it may vary during development, zebrafish embryos, eleutheroembryos, or larvae at 1, 2, 3, 4, 5, and 6 days post fertilization (dpf) were exposed to DMSO (0.1%), tert-butylhydroquinone (tBHQ; 10 ┬ÁM) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 2 nM) for 6 hr. Transcript abundance was assessed by real-time qRT-PCR and microarray. qRT-PCR showed strong (4- to 5-fold) induction of gstp1 by tBHQ as early as 1 dpf. tBHQ also induced gclc (2 dpf), but not sod1, nqo1, or cyp1a. TCDD induced cyp1a but none of the other genes. Microarray analysis showed that 1477 probes were significantly different among the DMSO-, tBHQ-, and TCDD-treated eleutheroembryos at 4 dpf. There was substantial overlap between genes induced in developing zebrafish and a set of marker genes induced by oxidative stress in mammals. Genes induced by tBHQ in 4-dpf zebrafish included those involved in glutathione synthesis and utilization, signal transduction, and DNA damage/stress response. The strong induction of hsp70 determined by microarray was confirmed by qRT-PCR and by use of transgenic zebrafish expressing enhanced green fluorescent protein (EGFP) under control of the hsp70 promoter. Genes strongly down-regulated by tBHQ included mitfa, providing a molecular explanation for the loss of pigmentation in tBHQ-exposed embryos. These data show that zebrafish embryos are responsive to oxidative stress as early as 1 dpf, that responsiveness varies with development in a gene-specific manner, and that the oxidative stress response is substantially conserved in vertebrate animals.
Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes