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Updated: Jul 5, 2026
In vitro Cell Culture Model for Toxic Inhaled Chemical Testing
Published on: May 8, 2014
Trichloroethylene disrupts cardiac gene expression and calcium homeostasis in rat myocytes
Patricia T Caldwell1, Patricia A Thorne, Paula D Johnson
1Department of Veterinary Science & Microbiology, University of Arizona, Tucson, Arizona 85721, USA.
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.
Insights
Trichloroethylene (TCE) exposure disrupts intracellular calcium (Ca2+) regulation in heart cells by reducing key protein expression. This calcium signaling disruption may explain TCE
Area of Science:
- Environmental Toxicology
- Cardiovascular Toxicology
- Developmental Biology
Background:
- Trichloroethylene (TCE) is a common environmental contaminant linked to cardiac malformations.
- Previous studies suggest TCE disrupts intracellular calcium ([Ca2+](i)) regulation in cardiac cells.
- Key proteins implicated include ryanodine receptor isoform 2 (Ryr2) and sarcoendoplasmatic reticulum Ca2+ ATPase (Serca2a).
Purpose of the Study:
- To investigate if TCE-induced gene expression changes in Ca2+-associated proteins alter Ca2+ flux regulation.
- To characterize the effects of TCE on gene expression and Ca2+ response in rat cardiac myocytes.
Main Methods:
- Real-time PCR was used to quantify gene expression levels.
- Digital imaging microscopy assessed Ca2+ responses to vasopressin (VP).
- Rat cardiac H9c2 myocytes were exposed to various TCE doses.
Main Results:
- TCE exposure significantly reduced Serca2a and Ryr2 expression at 12 and 48 hours.
- Altered Ca2+ responses to VP were observed in cells treated with TCE as low as 10 parts per billion.
- TCE exposure disrupts myocytes' ability to regulate cellular Ca2+ fluxes.
Conclusions:
- TCE exposure perturbs calcium signaling, affecting cardiac cell physiology and signal transduction.
- These findings suggest a mechanism for TCE-induced cardiac toxicity during embryonic development.
- Further in vivo studies are needed to confirm these cardio-specific toxic effects.
