Skip to main content
SpringerLink
Log in

Effects of low bisphenol A concentration on protein expression profiles in an in vitro model of non-alcoholic fatty liver disease

  • Original Paper
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

Bisphenol A (BPA) is an environmental toxicant that causes adverse effects to liver even at low concentrations. Non-alcoholic fatty liver disease (NAFLD) presents as significant accumulation of lipids in the liver, impairing detoxification processes. Nevertheless, little information is available regarding the susceptibility of NAFLD to BPA toxicity. Here, we compared the effects of low concentration BPA exposure on the protein profiles of normal and NAFLD cells. We established NAFLD model by treating HepG2 cells with fatty acids and subsequently treated with low BPA concentration. Protein expression profiles showed that four proteins from normal cells and nine proteins from NAFLD cells were dysregulated after BPA treatment. A pathway analysis revealed decreased expression of translation elongation factor proteins in NAFLD cells following BPA treatment and this down-regulation was confirmed by immunoblotting. Our findings suggest that BPA toxicity is more deleterious, especially to translation elongation, in NAFLD cells than normal cells.

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

References

  1. U.S. Environmental Protecting Agency. Bisphenol A Action Plan. Retrieved July 5th, 2016, from the U.S. Environmental Protecting Agency Website: https:// www.epa.gov/assessing-andmanaging-chemicalsunder-tsca/bisphenol-bpa-action-plan (2010).

  2. U.S. Food and Drug Administration. Update on Bisphenol A for Use in Food Contact Applications. Retrieved July 9th, 2016, from the U.S. Food and Drug Administration Website: http://www.fda.gov/News Events/PublicHealthFocus/ucm064437.htm (2010).

  3. Bureau of Chemical Safety, Food Directorate Health Products and Food Branch. Survey of Bisphenol A in Canned Food Products from Canadian Markets. Authority of the Minister of Health, Ottawa, Ontario (2010).

  4. Carwile, J. L. & Michels, K. B. Urinary bisphenol A and obesity: NHANES 2003-2006. Environ Res 111: 825–830 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Noonan, G. O., Ackerman, L. K. & Begley, T. H. Concentration of bisphenol A in highly consumed canned foods on the U.S. market. J Agric Food Chem 59: 7178–7185 (2011).

    Article  CAS  PubMed  Google Scholar 

  6. Huang, Y. Q. et al. Bisphenol A (BPA) in China: a review of sources, environmental levels, and potential human health impacts. Environ Int 42: 91–99 (2012).

    Article  CAS  PubMed  Google Scholar 

  7. Funabashi, T., Kawaguchi, M. & Kimura, F. The endocrine disruptors butyl benzyl phthalate and bisphenol A increase the expression of progesterone receptor messenger ribonucleic acid in the preoptic area of adult ovariectomized rats. Neuroendocrinology 74: 77–81 (2001).

    Article  CAS  PubMed  Google Scholar 

  8. Salian, S., Doshi, T. & Vanage, G. Neonatal exposure of male rats to bisphenol A impairs fertility and expression of Sertoli cell junctional proteins in the testis. Toxicology 265: 56–67 (2009).

    Article  CAS  PubMed  Google Scholar 

  9. Wu, J. H. et al. Oral exposure to low-dose bisphenol A aggravates testosterone-induced benign hyperplasia prostate in rats. Toxicol Ind Health 27: 810–819 (2011).

    Article  CAS  PubMed  Google Scholar 

  10. Tainaka, H. et al. Evaluation of the testicular toxicity of prenatal exposure to bisphenol A based on microarray analysis combined with MeSH annotation. J Toxicol Sci 37: 539–548 (2012).

    Article  CAS  PubMed  Google Scholar 

  11. Zhang, W. Z., Yong, L., Jia, X. D., Li, N. & Fan, Y. X. Combined subchronic toxicity of bisphenol A and dibutyl phthalate on male rats. Biomed Environ Sci 26: 63–69 (2013).

    PubMed  Google Scholar 

  12. Somm, E. et al. Perinatal exposure to bisphenol A alters early adipogenesis in the rat. Environ Health Perspect 117: 1549–1555 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hassan, Z. K. et al. Bisphenol A induces hepatotoxicity through oxidative stress in rat model. Oxid Med Cell Longev 2012: 194829 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Huc, L., Lemarie, A., Gueraud, F. & Helies-Toussaint, C. Low concentrations of bisphenol A induce lipid accumulation mediated by the production of reactive oxygen species in the mitochondria of HepG2 cells. Toxicol In Vitro 26: 709–717 (2012).

    Article  CAS  PubMed  Google Scholar 

  15. Shankar, A., Teppala, S. & Sabanayagam, C. Urinary bisphenol A levels and measures of obesity: results from the national health and nutrition examination survey 2003-2008. ISRN Endocrinol 2012: 965243 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bradley, E. L., Read, W. A. & Castle, L. Investigation into the migration potential of coating materials from cookware products. Food Addit Contam 24: 326–335 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Silver, M. K., O’Neill, M. S., Sowers, M. R. & Park, S. K. Urinary bisphenol A and type-2 diabetes in U.S. adults: data from NHANES 2003-2008. PLoS One 6: e26868 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Shankar, A. & Teppala, S. Urinary bisphenol A and hypertension in a multiethnic sample of US adults. J Environ Public Health 2012: 481641 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kovacic, P. How safe is bisphenol A? Fundamentals of toxicity: metabolism, electron transfer and oxidative stress. Med Hypotheses 75: 1–4 (2010).

    Article  CAS  PubMed  Google Scholar 

  20. Geens, T. et al. A review of dietary and non-dietary exposure to bisphenol-A. Food Chem Toxicol 50: 3725–3740 (2012).

    Article  CAS  PubMed  Google Scholar 

  21. Merrell, M. D. & Cherrington, N. J. Drug metabolism alterations in nonalcoholic fatty liver disease. Drug Metab Rev 43: 317–334 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. LaBrecque, D. Abbas et al. Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis (World Gastroenterology Organisation Global Guidelines. Milwaukee, MI, 2012).

    Google Scholar 

  23. Younossi, Z. M. et al. Global epidemiology of nonalcoholic fatty liver disease - meta-analytic assessment of prevalence, incidence and outcomes. Hepatology 64: 73–84 (2016).

    Article  PubMed  Google Scholar 

  24. Welshons, W. V., Nagal, S. C. & vom Saal, F. Large effects from small exposure. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Endocrinology 147:S56–69 (2006).

    Article  CAS  PubMed  Google Scholar 

  25. Cao, X. et al. Background bisphenol A in experimental materials and its implication to low-dose in vitro study. Chemosphere 81: 817–820 (2010).

    Article  CAS  PubMed  Google Scholar 

  26. Chavez-Tapia, N. C., Rosso, N. & Tiribelli, C. Effect of intracellular lipid accumulation in a new model of non-alcoholic fatty liver disease. BMC Gastroenterology 12: doi:10.1186/1471-230X-12-20 (2012).

  27. Cui, W., Chen, S. L. & Hu, K. Quantification and mechanisms of oleic acid-induced steatosis in HepG2 cells. Am J Transl Res 2: 95–104 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Garcia-Ruiz, I., Solis-Munoz, P., Fernandez-Moreira, D., Munoz-Yague, T. & Solis-Herruzo, J. A. In vitro treatment of HepG2 cells with saturated fatty acids reproduces mitochondrial dysfunction found in nonalcoholic steatohepatitis. Dis Model Mech 8: 183–191 (2015).

    Article  PubMed  Google Scholar 

  29. Tinaikos, D. G., Vos, M. B. & Brunt, E. M. Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol Mech Dis 5: 145–171 (2010).

    Article  Google Scholar 

  30. Lake, A. D. et al. Analysis of global and absorption, distribution, metabolism and elimination gene expression in the progressive stages of human nonalcoholic fatty liver disease. Drug Metab Dispos 39: 1954–1960 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yalcin, E. B., Kulkarni, S. R., Slitt, A. L. & King, R. Bisphenol A sulfonation is impaired in metabolic and liver disease. Toxicol Appl Pharmacol 292: 75–84 (2016).

    Article  CAS  PubMed  Google Scholar 

  32. Browne G. J. & Proud, C. G. Regulation of peptidechain elongation in mammalian cells. Eur J Biochem 269: 5360–5368 (2002).

    Article  CAS  PubMed  Google Scholar 

  33. Qiu, F. et al. Eukaryotic elongation factor-1α 2 knockdown inhibits hepatocarcinogenesis by suppressing PI3K/Akt/NF-κB signaling. World J Gastroenterol 22: 4226–4237 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Stoianov, A. M., Robson, D. L., Hetherington, A. M., Sawyez, C. G. & Borradaile, N. M. Elongation factor 1A-1 is a mediator if hepatocyte lipotoxicity partly through its canonical function in protein synthesis. PLoS One 10:e0131269 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Geldof, A. A., Mastbergen, S. C., Henrar, R. E. C. & Faircloth, G. T. Cytotoxicity and neurocytotoxicity of new marine anticancer agents evaluated using in vitro assays. Cancer Chemother Pharmacol 44: 312–318 (1999).

    Article  CAS  PubMed  Google Scholar 

  36. Kaul, G., Pattan, G. & Rafeequi, T. Eukaryotic elongation factor-2 (eEF2): its regulation and peptide chain elongation. Cell Biochem Funct 29: 227–234 (2011).

    Article  CAS  PubMed  Google Scholar 

  37. Nakamura, J. et al. Overexpression of eukaryotic elongation factor eEF2 in gastrointestinal cancers and its involvement in G2/M progression in the cell cycle. Int J Oncol 34: 1181–1189 (2009).

    CAS  PubMed  Google Scholar 

  38. Lindqvist, L. et al. Inhibition of translation by cytotrienin A - a member of the ansamycin family. RNA 16: 2404–2413 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zhong, J. et al. Transfer RNAs mediate the rapid adaptation of Escherichia coli to oxidative stress. PLoS Genet 11:e1005320 (2015).

    Article  Google Scholar 

  40. Nakamura, M. et al. Phosphoproteomic profiling of human SH-SY5Y neuroblastoma cells during response to 6-hydroxydopamine-induced oxidative stress. Biochim Biophys Acta 1763: 977–989 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Parrado, J., Absi, E. H., Machado, A. & Ayala, A. “In vitro” effect of cumene hydroperoxide on hepatic elongation factor-2 and its protection by melatonin. Biochim Biophys Acta 1624: 139–144 (2003).

    Article  CAS  PubMed  Google Scholar 

  42. Arguelles, S., Machado, A. & Ayala, A. “In vitro” effect of lipid peroxidation metabolites on elongation factor-2. Biochim Biophys Acta 1760: 445–452 (2006).

    Article  PubMed  Google Scholar 

  43. Moon, M. K. et al. Bisphenol A impairs mitochondrial function in the liver at doses below the no observed adverse effect level. J Korean Med Sci 27: 644–652 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Boucher, J. G. et al. Identification of mechanisms of action of bisphenol A-induced human preadipocyte differentiation by transcriptional profiling. Obesity 22: 2333–2343 (2014).

    Article  CAS  PubMed  Google Scholar 

  45. GoodsonIII, W. H. et al. Activation of the mTOR pathway by low levels of xenoestrogens in breast epithelial cells from high-risk women. Carcinogenesis 32: 1724–1733 (2011).

    Article  Google Scholar 

  46. Ribeiro-Varandas, E. et al. Bisphenol A disrupts transcription and decreases viability in aging vascular endothelial cells. Int J Mol Sci 15: 15791–15805 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Huang, K. & Fingar, D. C. Growing knowledge of the mTOR signaling network. Semin Cell Dev Biol 36: 79–90 (2014).

    Article  PubMed  Google Scholar 

  48. Parkhitko, A. A., Favorova, O. O., Khabibullin, D. I., Anisimov, V. N. & Henske, E. P. Kinase mTOR: Regulation and role in maintenance of cellular homeostasis, tumor development and aging. Biochemistry (Mosc) 79: 88–101 (2014).

    Article  CAS  Google Scholar 

  49. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55–63 (1983).

    Article  CAS  PubMed  Google Scholar 

  50. Reamtong, O. et al. Protein profiling of mefloquine resistant Plasmodium falciparum using mass spectrometry-based proteomics. Int J Mass Spectrom 391: 82–92 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

    Peerut Chienwichai, Suwalee Worakhunpiset & Prapin Tharnpoophasiam

  2. Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

    Supachai Topanurak, Onrapak Reamtong & Usa Boonyuen

  3. Center of Excellence for Antibody Research, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

    Supachai Topanurak

Authors
  1. Peerut Chienwichai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Supachai Topanurak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Onrapak Reamtong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Usa Boonyuen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Suwalee Worakhunpiset
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Prapin Tharnpoophasiam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Prapin Tharnpoophasiam.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chienwichai, P., Topanurak, S., Reamtong, O. et al. Effects of low bisphenol A concentration on protein expression profiles in an in vitro model of non-alcoholic fatty liver disease. Mol. Cell. Toxicol. 14, 61–70 (2018). https://doi.org/10.1007/s13273-018-0008-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-018-0008-2

Keywords

Search

Navigation