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

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 def...

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Autores principales: Hahn, Mark E., McArthur, Andrew G., Karchner, Sibel I., Franks, Diana G., Jenny, Matthew J., Timme-Laragy, Alicia R., Stegeman, John J., Woodin, Bruce R., Cipriano, Michael J., Linney, Elwood
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234671/
https://www.ncbi.nlm.nih.gov/pubmed/25402455
http://dx.doi.org/10.1371/journal.pone.0113158
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author Hahn, Mark E.
McArthur, Andrew G.
Karchner, Sibel I.
Franks, Diana G.
Jenny, Matthew J.
Timme-Laragy, Alicia R.
Stegeman, John J.
Woodin, Bruce R.
Cipriano, Michael J.
Linney, Elwood
author_facet Hahn, Mark E.
McArthur, Andrew G.
Karchner, Sibel I.
Franks, Diana G.
Jenny, Matthew J.
Timme-Laragy, Alicia R.
Stegeman, John J.
Woodin, Bruce R.
Cipriano, Michael J.
Linney, Elwood
author_sort Hahn, Mark E.
collection PubMed
description 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 µM) 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.
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spelling pubmed-42346712014-11-21 The Transcriptional Response to Oxidative Stress during Vertebrate Development: Effects of tert-Butylhydroquinone and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Hahn, Mark E. McArthur, Andrew G. Karchner, Sibel I. Franks, Diana G. Jenny, Matthew J. Timme-Laragy, Alicia R. Stegeman, John J. Woodin, Bruce R. Cipriano, Michael J. Linney, Elwood PLoS One Research Article 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 µM) 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. Public Library of Science 2014-11-17 /pmc/articles/PMC4234671/ /pubmed/25402455 http://dx.doi.org/10.1371/journal.pone.0113158 Text en © 2014 Hahn et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hahn, Mark E.
McArthur, Andrew G.
Karchner, Sibel I.
Franks, Diana G.
Jenny, Matthew J.
Timme-Laragy, Alicia R.
Stegeman, John J.
Woodin, Bruce R.
Cipriano, Michael J.
Linney, Elwood
The Transcriptional Response to Oxidative Stress during Vertebrate Development: Effects of tert-Butylhydroquinone and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin
title The Transcriptional Response to Oxidative Stress during Vertebrate Development: Effects of tert-Butylhydroquinone and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin
title_full The Transcriptional Response to Oxidative Stress during Vertebrate Development: Effects of tert-Butylhydroquinone and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin
title_fullStr The Transcriptional Response to Oxidative Stress during Vertebrate Development: Effects of tert-Butylhydroquinone and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin
title_full_unstemmed The Transcriptional Response to Oxidative Stress during Vertebrate Development: Effects of tert-Butylhydroquinone and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin
title_short The Transcriptional Response to Oxidative Stress during Vertebrate Development: Effects of tert-Butylhydroquinone and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin
title_sort transcriptional response to oxidative stress during vertebrate development: effects of tert-butylhydroquinone and 2,3,7,8-tetrachlorodibenzo-p-dioxin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234671/
https://www.ncbi.nlm.nih.gov/pubmed/25402455
http://dx.doi.org/10.1371/journal.pone.0113158
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