| Blocking expression of AHR2 and ARNT1 in zebrafish larvae protects against cardiac toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. | |
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MedLine Citation:
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PMID: 16936225 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The zebrafish (Danio rerio) has become an attractive vertebrate model for studying developmental processes, and is emerging as a model system for studying the mechanisms by which xenobiotic compounds perturb normal development. Embryos treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) shortly after fertilization exhibit a range of adverse effects on the heart: an early reduction in cardiac myocyte number, followed by a change in heart looping and morphology, with an apparent compaction of the ventricle and overall decrease in heart size. These changes are accompanied by impaired cardiac function including a decrease in cardiac output and eventually irreversible ventricular standstill. The mechanisms involved in mediating effects of TCDD on the heart remain unknown. However, it is widely accepted that aryl hydrocarbon receptor (AHR) activation mediates endpoints of TCDD toxicity in vertebrates. In zebrafish, there are multiple forms of AHR and AHR nuclear translocator protein (ARNT) raising the question about whether different endpoints of TCDD toxicity are mediated by different components of the AHR/ARNT pathway. To address this question we used morpholino oligonucleotide technology to specifically block the expression of zfAHR2, zfARNT1, zfARNT2, and zfCYP1A, and assessed the previously described effects of TCDD on heart morphology, size, and function in the developing morphants. We report that blocking zfAHR2 and zfARNT1 expression provided protection against the TCDD-mediated alteration in heart morphology, reduced cardiac myocyte number, decreased cardiac output and ventricular standstill in zebrafish larvae, while the zfarnt2 and zfcyp1a morpholinos did not block the TCDD-induced cardiac toxicity. |
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Authors:
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Dagmara S Antkiewicz; Richard E Peterson; Warren Heideman |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2006-08-25 |
Journal Detail:
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Title: Toxicological sciences : an official journal of the Society of Toxicology Volume: 94 ISSN: 1096-6080 ISO Abbreviation: Toxicol. Sci. Publication Date: 2006 Nov |
Date Detail:
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Created Date: 2006-10-05 Completed Date: 2007-03-13 Revised Date: 2010-09-17 |
Medline Journal Info:
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Nlm Unique ID: 9805461 Medline TA: Toxicol Sci Country: United States |
Other Details:
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Languages: eng Pagination: 175-82 Citation Subset: IM |
Affiliation:
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Molecular and Environmental Toxicology Center, Madison, Wisconsin, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aryl Hydrocarbon Receptor Nuclear Translocator / antagonists & inhibitors, genetics*, metabolism Gene Expression Regulation, Developmental / drug effects, genetics Heart Block / chemically induced, genetics, prevention & control Heart Defects, Congenital / chemically induced, genetics, prevention & control* Larva / drug effects, genetics Myocytes, Cardiac / drug effects Oligonucleotides, Antisense / administration & dosage, genetics Protein Isoforms / antagonists & inhibitors, genetics, metabolism Receptors, Aryl Hydrocarbon / antagonists & inhibitors, genetics*, metabolism Stroke Volume / drug effects Tetrachlorodibenzodioxin / toxicity* Time Factors Ventricular Function / drug effects Zebrafish / genetics* Zebrafish Proteins / antagonists & inhibitors, genetics*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 ES012716/ES/NIEHS NIH HHS; T32 ES07015/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/AHR2 protein, zebrafish; 0/Oligonucleotides, Antisense; 0/Protein Isoforms; 0/Receptors, Aryl Hydrocarbon; 0/Zebrafish Proteins; 0/arnt1a protein, zebrafish; 138391-32-9/Aryl Hydrocarbon Receptor Nuclear Translocator; 1746-01-6/Tetrachlorodibenzodioxin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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