Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Trichloroethylene disrupts cardiac gene expression and calcium homeostasis in rat myocytes.

Authors: Caldwell, Patricia T; Thorne, Patricia A; Johnson, Paula D; Boitano, Scott; Runyan, Raymond B; Selmin, Ornella

Published In Toxicol Sci, (2008 Jul)

Abstract: We have been investigating the molecular mechanisms by which trichloroethylene (TCE) might induce cardiac malformations in the embryonic heart. Previous results indicated that TCE disrupted expression of genes encoding proteins involved in regulation of intracellular Ca2+, [Ca2+](i), in cardiac cells, including ryanodine receptor isoform 2 (Ryr2), and sarcoendoplasmatic reticulum Ca2+ ATPase, Serca2a. These observations are important in light of the notion that altered cardiac contractility can produce morphological defects. The hypothesis tested in this study is that the TCE-induced changes in gene expression of Ca2+-associated proteins resulted in altered Ca2+ flux regulation. We used real-time PCR and digital imaging microscopy to characterize effects of various doses of TCE on gene expression and Ca2+ response to vasopressin (VP) in rat cardiac H9c2 myocytes. We observed a reduction in Serca2a and Ryr2 expression at 12 and 48 h after exposure to TCE. In addition, we found significant differences in Ca2+ response to VP in cells treated with TCE doses as low as 10 parts per billion. Taken all together, our data strongly indicate that exposure to TCE disrupts the ability of myocytes to regulate cellular Ca2+ fluxes. Perturbation of calcium signaling alters cardiac cell physiology and signal transduction and may hint to morphogenetic consequences in the context of heart development. These results point to a novel area of TCE biology and, if confirmed in vivo, may help to explain the apparent cardio-specific toxicity of TCE exposure in the rodent embryo.

PubMed ID: 18411232 Exiting the NIEHS site

MeSH Terms: Animals; Calcium/metabolism*; Cell Line; Gene Expression/drug effects; Homeostasis; Myocardium/metabolism*; Myocytes, Cardiac/drug effects*; Myocytes, Cardiac/metabolism; RNA, Messenger/metabolism; Rats; Ryanodine Receptor Calcium Release Channel/genetics; Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics; Signal Transduction/drug effects; Solvents/toxicity*; Trichloroethylene/toxicity*

Back
to Top