Trichloroethylene and trichloroacetic acid regulate calcium signaling pathways in murine embryonal carcinoma cells p19.
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.
Selmin
Ornella I
OI
Department of Veterinary Science and Microbiology, University of Arizona, 1117 E. Lowell St., Building 90, Room CAF14, Tucson, AZ, 85721-210090, USA. selmin@u.arizona.edu
Thorne
Patricia A
PA
Caldwell
Patricia T
PT
Taylor
Mallory R
MR
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects* / Q000235:genetics; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D054278:Embryonal Carcinoma Stem Cells / Q000187:drug effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D013997:Time Factors; D014238:Trichloroacetic Acid / Q000633:toxicity*; D014241:Trichloroethylene / Q000633:toxicity*
D004785:Environmental Pollutants; D019837:Ryanodine Receptor Calcium Release Channel; D014241:Trichloroethylene; D014238:Trichloroacetic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517674:Camk2g protein, mouse