Trichloroethylene and Trichloroacetic Acid Regulate Calcium Signaling Pathways in Murine Embryonal Carcinoma Cells P19
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Trichloroethylene (TCE) and its metabolite trichloroacetic acid (TCA) are ubiquitous environmental contaminants which have been regarded as risk factors for congenital heart malformations. An increasing body of evidence from in vivo and in vitro studies supports the notion that exposure to TCE and TCA may interfere with normal embryonic heart development. The expression of several genes coding for factors implicated in the regulation of cardiac development has been shown to be modified by TCE or TCA, but the molecular mechanisms that mediate these effects are still obscure. In this study, we investigated the global changes in gene expression caused by exposure of P19 embryonal carcinoma cells to TCE and TCA, and whether or not TCE and/or TCA influence the expression levels of genes encoding for proteins that regulate calcium fluxes in cardiac cells. We report that TCE and TCA disrupt the expression of genes involved in processes important during embryonic development suggesting that exposure to environmentally significant concentrations of TCE may have deleterious effects on specific stages of cardiac differentiation.
KeywordsCalcium/calmodulin-dependent protein kinase Embryonic development Environmental toxicant Gene expression Rynodine receptor
This research was supported by NIH, SBPR Program No. P42ES04940. Thanks to GE Healthcare Codelink for the microarrays, to George Watts of the Microarray Facility and BioInformatic Service of the SWEHSC (NIH, NIEHS Grant No. ES06694), University of Arizona for carrying out the microarray analysis and help in analyzing the data. Thanks to the Honors College of the University of Arizona, for supporting MT.
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