Skip to main content
SpringerLink
Log in

Effects of trichloroethylene and its metabolite trichloroacetic acid on the expression of vimentin in the rat H9c2 cell line

  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

Trichloroethylene (TCE) and its metabolite trichloroacetic acid (TCAA) are environmental contaminants with specific toxicity for the embryonic heart. In an effort to identify the cellular pathways disrupted by TCE and TCAA during heart development, we investigated their effects on expression of vimentin, a marker of cardiac differentiation. Previous studies had shown that the level of vimentin transcript was inhibited in rat embryonic heart after maternal exposure to TCE via drinking water. In the same study, maternal exposure to TCAA produced the opposite effect, inducing an increased level of vimentin mRNA. In this study, we selected an in vitro system, the rat cardiac myoblast cell line H9c2, to further characterize the molecular mechanisms used by TCE and TCAA to disrupt normal heart development. In particular, we investigated the effects of both toxicants on vimentin, at both the RNA and protein levels, using dose–response and time course curves. Our experimental findings indicate that vimentin expression is affected by TCE and TCAA in H9c2 cells similarly as in vivo. The work is significant because it provides a suitable in vitro model for studies looking at toxicant effects on myocardiac cells, and it suggests that vimentin is a good marker of TCE exposure in the embryonic heart.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ALDH1:

aldehyde dehhydrogenase 1

AV:

atrioventricular

DCE:

dichloroethylene

EMT:

epithelial–mesenchymal transition

PEITC:

phenethyl isothiocyanate

SSH:

select subtractive hybridization

TCAA:

trichloroacetic acid

TCE:

trichloroethylene

TCEtOH:

trichloroethanol

References

  • Bove FJ, Fulcomer MC, Klotz JB, Esmart J, Dufficy EM, Savrin JE. Public drinking water contamination and birth outcomes. Am J Epidemiol. 1995;141:850–62.

    PubMed  Google Scholar 

  • Boyer AS, Finch WT, Runyan RB. Trichloroethylene inhibits development of embryonic heart valve precursors in vitro. Toxicol Sci. 2000;53:109–17.

    Article  PubMed  Google Scholar 

  • Brauer PR, Rosenquist TH. Effect of elevated homocysteine on cardiac neural crest migration in vitro. Dev Dyn. 2002;224:222–30.

    Article  PubMed  Google Scholar 

  • Chae H, So H, Chae S, et al. Sodium nitroprusside induces apoptosis of H9C2 cardiac muscle cells in a c-Jun N-terminal kinase-dependent manner. Int Immunopharmacol. 2001;1:967–78.

    Article  PubMed  Google Scholar 

  • Chen F, Chang R, Trivedi M, Capetanaki Y, Cryns V. Caspase proteolysis of desmin produces a dominant-negative inhibitor of intermediate filaments and promotes apoptosis. J Biol Chem. 2003;278(9):6848–53.

    Article  PubMed  Google Scholar 

  • Collier JM, Cover CC, Selmin O, Johnson PD, Runyan RB. Trichloroethylene effects on gene expression during cardiac development. Birth Defects Res Part A Clin Mol Teratol. 2003;67:488–95.

    Article  Google Scholar 

  • Collins MD, Mao GE. Teratology of retinoids. Annu Rev Pharmacol Toxicol. 1999;39:399–430.

    Article  PubMed  Google Scholar 

  • Creazzo TL, Godt RE, Leatherbury L, Conway SJ, Kirby ML. Role of cardiac neural crest cells in cardio-vascular development. Annu Rev Physiol. 1998;60:267–86.

    Article  PubMed  Google Scholar 

  • Davidson IWF, Beliles RP. Consideration of the target organ toxicity of trichloroethylene in terms of metabolite toxicity and pharmacokinetics. Drug Metab Rev. 1991;23:493–599.

    PubMed  Google Scholar 

  • Dawson BV, Johnson PD, Goldberg SJ, Ulreich JB. Cardiac teratogenesis of trichloroethylene and dichloroethylene in a mammalian model. J Am Coll Cardiol. 1990;16(5):1304–9.

    PubMed  Google Scholar 

  • Dawson BV, Johnson PD, Goldberg SJ, Ulreich JB. Cardiac teratogenesis of halogenated hydrocarbon-contaminated drinking water. J Am Coll Cardiol. 1993;21(6):1466–72.

    PubMed  Google Scholar 

  • Epstein RM, Papper EM. Respiratory factors in the uptake and excretion of anesthetics. Int Anesthesiol Clin. 1998;36(4):121–35.

    PubMed  Google Scholar 

  • Fisher JW, Channel SR, Eggers JS, et al. Trichloroethylene, trichloroacetic acid, and dichloroethylene: do they affect fetal rat heart development? Int J Toxicol. 2001;20(5):257– 67.

    Article  PubMed  Google Scholar 

  • Ghantous H, Danielsson BR, Dencker L, Gorczak J, Vesterberg O. Trichloroacetic acid accumulates in murine amniotic fluid after tri- and tetrachloroethylene inhalation. Acta Pharmacol Toxicol (Copenh). 1986;58(2):105–14.

    Google Scholar 

  • Goldberg SJ, Lebowitz MD, Graver EJ, Hicks S. The association of human congenital cardiac malformations and drinking water contaminants. J Am Coll Cardiol. 1990;16(1):155–64.

    PubMed  Google Scholar 

  • Goldberg SJ, Dawson BV, Johnson, PD, Hoyme HE, Ulreich JB. Cardiac teratogenicity of dichloroethylene in a chick model. Pediatr Res. 1992;32(1):23–6.

    PubMed  Google Scholar 

  • Haselbeck RJ, Hoffmann I, Duester G. Distinct functions for ALDH1 and Raldh2 in the control of ligand production for embryonic retinoid signaling pathway. Dev Genet. 1999;25:353–64.

    Article  PubMed  Google Scholar 

  • Helliwell PJ, Hutton AM. Trichloroethylene anaesthesia. 1. Distribution in the foetal and maternal circulation of pregnant sheep and goats. Anaesthesia. 1950;5:4–13.

    Google Scholar 

  • Hendrix MJC, Seftor EA, Seftor REB, Trevor KT. Experimental co-expression of vimentin and keratin intermediate filaments in human breast cancer cells results in phenotypic interconversion and increased invasive behaviour. Am J Pathol. 1997;150:483–95.

    PubMed  Google Scholar 

  • Hengstschlager M, Rosner M, Fountoulakis M, Oh J, Lubec G. Protein levels of α1-tubulin, protein disulfide isomerase, tropomyosin and vimentin are regulated by the tuberous sclerosis gene products. Cancer Lett. 2004;210:219–26.

    Article  PubMed  Google Scholar 

  • Johnson PD, Dawson BV, Goldberg SJ. Cardiac teratogenicity of trichloroethylene metabolites. J Am Coll Cardiol. 1998;32(2):540–5.

    Article  PubMed  Google Scholar 

  • Kashour T, Burton T, Dibrov A, Amara F. Myogenic signaling by lithium in cardiomyoblasts is Akt independent but requires activation of the β -catenin-Tcf/Lef pathway. J Mol Cell Cardiol. 2003;35:937–51.

    Article  PubMed  Google Scholar 

  • Kirby ML. Cardiac morphogenesis–research advances. Pediatr Res. 1987;21(3):219–24.

    PubMed  Google Scholar 

  • Kirby ML, Waldo KL. Neural crest and cardiovascular patterning. Circ Res. 1995;77:211–5.

    PubMed  Google Scholar 

  • Laham S. Studies on placental transfer of trichloroethylene. Ind Med. 1980;39:46.

    Google Scholar 

  • Li J, Molkentin JD, Colbert MC. Retinoic acid inhibits cardiac neural crest migration by blocking c-jun N-terminal kinase activation. Dev Biol. 2001;232:351–61.

    Article  PubMed  Google Scholar 

  • Menard C, Pupier S, Mornet D, Kitzmann M, Nargeot J, Lory P. Modulation of L-type calcium channel expression during retinoic acid-induced differentiation of H9c2 cardiac cells. J Biol Chem. 1999;274(41):29063–70.

    Article  PubMed  Google Scholar 

  • Moreno RL, Goosen T, Kent UM, Chung FL, Hollenberg PF. Differential effects of naturally occurring isothiocyanates on the activities of cytochrome P4502E1 and the mutant P4502E1 T303A. Arch Biochem Byophys. 2001;391(1):99– 110.

    Article  Google Scholar 

  • Nakajiama M, Yoshida R, Shimada N, Yamazaki H, Yokoi T. Inhibition and inactivation of human cytochrome P450 isoforms by phenethyl isothiocyanate. Drug Metab Dispos. 2001;29(8);1110–3.

    PubMed  Google Scholar 

  • Nelson AN, Lipsky JJ. Microtiter plate based determination of multiple concentration–inhibition relationships. Anal Biochem. 1995;231:437–9.

    Article  PubMed  Google Scholar 

  • Ou J, Ou Z, McCarver DG et al. Trichloroethylene decreases heat shock protein 90 interactions with endothelial nitric oxide synthase:implications for endothelial cell proliferation. Toxicol Sci. 2003;73:90–7.

    Article  PubMed  Google Scholar 

  • Pereira MA, Kramer PM, Conran PB, Tao L. Effect of chloroform on dichloroacetic acid and trichloroacetic acid-induced hypomethylation and expression of the c-myc gene and on their promotion of liver and kidney tumors in mice. Carcinogenesis. 2001;22(9):1511–9.

    Article  PubMed  Google Scholar 

  • Song JZ, Ho JW. Simultaneous detection of trichloroethylene alcohol and acetate in rat urine by gas chromatography–mass spectrometry. J Chromatogr B. 2003;789(2):303–9.

    Article  Google Scholar 

  • Waldo KL, Kumishi D, Kirby ML. Cardiac neural crest is essential for the persistence rather than the formation of an arch artery. Dev Dyn. 1996;205:281–92.

    Article  PubMed  Google Scholar 

  • Wang J-L, Chen W-L, Tsai S-Y, Sung P-Y, Huang R-N. An in vitro model for evaluation of vaporous toxicity of trichloroethylene and tetrachloroethylene to CHO-K1 cells. Chem-Biol Interact. 2001;137:139–54.

    Article  PubMed  Google Scholar 

  • Yauck JS, Malloy ME, Blair K, Simpson PM, McCarver DG. Proximity of residence to trichloroethylene-emitting sites and increased risk of offspring congenital heart defects among older women. Birth Defects Res. (Part A) Clin Mol Teratol. 2004;70:808– 14.

    Article  Google Scholar 

  • Yoon W-H, Song I-S, Lee B-H, et al. Differential regulation of vimentin mRNA by 12-O-tetradecanoylphorbol 13-acetate and all-trans-retinoic acid correlates with motility of Hep 3B human hepatocellular carcinoma cells. Cancer Lett. 2004;2013:99–105.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Veterinary Sciences and Microbiology, University of Arizona, Tucson, Arizona, USA

    O. Selmin & P. T. Caldwell

  2. Department of Animal Care Facility, University of Arizona, Tucson, Arizona, USA

    P. A. Thorne & P. D. Johnson

  3. Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona, USA

    R. B. Runyan

  4. Department of Veterinary Sciences and Microbiology, University of Arizona, PO Box 210090, Tucson, AZ, 85721-0090, USA

    O. Selmin

Authors
  1. O. Selmin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. A. Thorne
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. T. Caldwell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. D. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. B. Runyan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O. Selmin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Selmin, O., Thorne, P.A., Caldwell, P.T. et al. Effects of trichloroethylene and its metabolite trichloroacetic acid on the expression of vimentin in the rat H9c2 cell line. Cell Biol Toxicol 21, 83–95 (2005). https://doi.org/10.1007/s10565-005-0124-3

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-005-0124-3

Keywords

Search

Navigation