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

Toxicological Sciences : an Official Journal of the Society of Toxicology
Patricia T CaldwellOrnella Selmin

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. Perturbati...Continue Reading

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Citations

Mar 26, 2011·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Sherif Hanafy, Fakhreddin Jamali
Apr 12, 2011·Cardiovascular Toxicology·Brittany PalbykinOrnella I Selmin
Nov 17, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Echoleah S RuferSusan M Smith
Dec 20, 2012·Environmental Health Perspectives·Weihsueh A ChiuJane C Caldwell
Oct 9, 2009·Birth Defects Research. Part A, Clinical and Molecular Teratology·Patricia T CaldwellOrnella Selmin
Jan 1, 2015·Reproductive Toxicology·Xin ChengXuesong Yang
Aug 31, 2016·Reproductive Toxicology·Susan L MakrisMichael G Narotsky
Aug 7, 2019·Birth Defects Research·Raymond B RunyanJennifer L Freeman
Oct 19, 2017·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·M E AbdrabohN M Eldeen
Mar 12, 2020·Environmental Science. Processes & Impacts·Sheri ChenRaymond B Runyan
Jan 7, 2018·Toxicology Letters·Alondra P HarrisRaymond B Runyan

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