| Exposure to low-dose trichloroethylene alters shear stress gene expression and function in the developing chick heart. | |
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MedLine Citation:
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PMID: 20186580 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Trichloroethylene is an organic solvent used as an industrial degreasing agent. Due to its widespread use and volatile nature, TCE is a common environmental contaminant. Trichloroethylene exposure has been implicated in the etiology of heart defects in human populations and animal models. Recent data suggest misregulation of Ca2+ homeostasis in H9c2 cardiomyocyte cell line after TCE exposure. We hypothesized that misregulation of Ca2+ homeostasis alters myocyte function and leads to changes in embryonic blood flow. In turn, changes in cardiac flow are known to cause cardiac malformations. To investigate this hypothesis, we dosed developing chick embryos in ovo with environmentally relevant doses of TCE (8 and 800 ppb). RNA was isolated from control and treated embryos at specific times in development for real-time PCR analysis of blood flow markers. Effects were observed on Endothelin-1 (ET-1), Nitric Oxide Synthase-3 (NOS-3) and Krüppel-like Factor 2 (KLF2) expression relative to TCE exposure and consistent with reduced flow. Further, we measured function in the developing heart after TCE exposure by isolating cardiomyocytes and measuring half-width of contraction and sarcomere lengths. These functional data showed a significant increase in half-width of contraction after TCE exposure. These data suggest that perturbation of cardiac function contributes to the etiology of congenital heart defects in TCE-exposed embryos. |
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Authors:
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Om Makwana; Nicholas M P King; Lauren Ahles; Ornella Selmin; Henk L Granzier; Raymond B Runyan |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cardiovascular toxicology Volume: 10 ISSN: 1559-0259 ISO Abbreviation: Cardiovasc. Toxicol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-14 Completed Date: 2010-10-19 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 101135818 Medline TA: Cardiovasc Toxicol Country: United States |
Other Details:
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Languages: eng Pagination: 100-7 Citation Subset: IM |
Affiliation:
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Department of Cell Biology and Anatomy, University of Arizona, 1501 N Campbell Avenue, PO Box 245044, Tucson, AZ 85724-5044, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Markers / metabolism Blood Flow Velocity Chick Embryo Dose-Response Relationship, Drug Embryo, Nonmammalian / drug effects*, metabolism Endothelin-1 / genetics, metabolism Gene Expression / drug effects* Heart / drug effects*, embryology Kruppel-Like Transcription Factors / genetics, metabolism Myocytes, Cardiac / drug effects, pathology, physiology Nitric Oxide Synthase Type III / genetics, metabolism Solvents / toxicity* Stress, Mechanical Teratogens / toxicity* Trichloroethylene / toxicity* |
| Grant Support | |
ID/Acronym/Agency:
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ES006694/ES/NIEHS NIH HHS; P30 ES006694-10/ES/NIEHS NIH HHS; R01 HL082851-04/HL/NHLBI NIH HHS; T32 HL007955-10/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Endothelin-1; 0/Kruppel-Like Transcription Factors; 0/Solvents; 0/Teratogens; 79-01-6/Trichloroethylene; EC 1.14.13.39/Nitric Oxide Synthase Type III |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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