| Role of zebrafish cytochrome P450 CYP1C genes in the reduced mesencephalic vein blood flow caused by activation of AHR2. | |
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MedLine Citation:
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PMID: 21504756 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes various signs of toxicity in early life stages of vertebrates through activation of the aryl hydrocarbon receptor (AHR). We previously reported a sensitive and useful endpoint of TCDD developmental toxicity in zebrafish, namely a decrease in blood flow in the dorsal midbrain, but downstream genes involved in the effect are not known. The present study addressed the role of zebrafish cytochrome P450 1C (CYP1C) genes in association with a decrease in mesencephalic vein (MsV) blood flow. The CYP1C subfamily was recently discovered in fish and includes the paralogues CYP1C1 and CYP1C2, both of which are induced via AHR2 in zebrafish embryos. We used morpholino antisense oligonucleotides (MO or morpholino) to block initiation of translation of the target genes. TCDD-induced mRNA expression of CYP1Cs and a decrease in MsV blood flow were both blocked by gene knockdown of AHR2. Gene knockdown of CYP1C1 by two different morpholinos and CYP1C2 by two different morpholinos, but not by their 5 nucleotide-mismatch controls, was effective in blocking reduced MsV blood flow caused by TCDD. The same CYP1C-MOs prevented reduction of blood flow in the MsV caused by β-naphthoflavone (BNF), representing another class of AHR agonists. Whole-mount in situ hybridization revealed that mRNA expression of CYP1C1 and CYP1C2 was induced by TCDD most strongly in branchiogenic primordia and pectoral fin buds. In situ hybridization using head transverse sections showed that TCDD increased the expression of both CYP1Cs in endothelial cells of blood vessels, including the MsV. These results indicate a potential role of CYP1C1 and CYP1C2 in the local circulation failure induced by AHR2 activation in the dorsal midbrain of the zebrafish embryo. |
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Authors:
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Akira Kubota; John J Stegeman; Bruce R Woodin; Toshihiko Iwanaga; Ryo Harano; Richard E Peterson; Takeo Hiraga; Hiroki Teraoka |
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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 Date: 2011-04-12 |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: 253 ISSN: 1096-0333 ISO Abbreviation: Toxicol. Appl. Pharmacol. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-05-27 Completed Date: 2011-07-26 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 244-52 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Toxicology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu 069-8501, Japan. akubota@whoi.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cytochrome P-450 Enzyme System / genetics, physiology* Gene Expression Regulation, Developmental Mesencephalon / blood supply* Protein Biosynthesis / drug effects Receptors, Aryl Hydrocarbon / physiology* Regional Blood Flow Tetrachlorodibenzodioxin / toxicity Zebrafish / embryology, genetics* Zebrafish Proteins / physiology* beta-Naphthoflavone / toxicity |
| Grant Support | |
ID/Acronym/Agency:
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5P42ES007381/ES/NIEHS NIH HHS; R01 ES015912-05/ES/NIEHS NIH HHS; R01ES015912/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/AHR2 protein, zebrafish; 0/Receptors, Aryl Hydrocarbon; 0/Zebrafish Proteins; 1746-01-6/Tetrachlorodibenzodioxin; 6051-87-2/beta-Naphthoflavone; 9035-51-2/Cytochrome P-450 Enzyme System |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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