Trichloroethylene induces methylation of the Serca2 promoter in H9c2 cells and embryonic heart

Brittany Palbykin, Jamie Borg, Patricia T. Caldwell, Josh Rowles, Andreas J. Papoutsis, Donato F. Romagnolo, Ornella I. Selmin

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Trichloroethylene (TCE) is a halogenated hydrocarbon used as a solvent in industrial settings and in house-cleaning products. Exposure to TCE has been linked to increased risk for congenital heart malformations in both human and animal models. Previous studies showed TCE exposure reduced the expression and function of the ATPdependent calcium pump, Serca2a, which is important for regulating calcium flux in myocytes and maintaining physiological cardiac function. In this study, we investigated whether TCE reduced Serca2a expression by altering the methylation status of its proximal promoter region. Low doses of TCE exposure (10 ppb) induced DNA hyper methylation in the Serca2 promoter region in cardiac myoblast cells and rat embryonic cardiac tissue. TCE exposure induced DNA methylation in a region of the Serca2 promoter which is the target for SP1 binding site essential for regulation of Serca2a transcriptional activity. Chromatin immunoprecipitation data confirmed that TCE exposure reduced the binding of SP1 to the Serca2 promoter region adjacent to the methylated CpG dimer. Finally, low-dose TCE exposure reduced the concentration of S-adenosyl-methionine in exposed cells and embryos. These cumulative data indicate that epigenetic mechanisms, including DNA methylation, may be important in mediating the teratogenic effects of TCE in embryonic heart.

Original languageEnglish (US)
Pages (from-to)204-214
Number of pages11
JournalCardiovascular toxicology
Volume11
Issue number3
DOIs
StatePublished - Sep 1 2011

Keywords

  • Cardiac development
  • DNA methylation
  • Epigenetic
  • S-adenosyl-methionine
  • Serca2
  • Trichloroethylene

ASJC Scopus subject areas

  • Molecular Biology
  • Toxicology
  • Cardiology and Cardiovascular Medicine

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