Advertisement

Perfluorinated compounds binding to estrogen receptor of different species: a molecular dynamic modeling

  • Kaili Qu
  • Juanjuan Song
  • Yu Zhu
  • Yaquan Liu
  • Chunyan Zhao
Original Paper
  • 20 Downloads

Abstract

Perfluorinated compounds (PFCs) were widely utilized in commercial and industrial applications, which could interfere with the endocrine systems of experimental animals and humans by interacting with estrogen receptors (ERs). Considering the possible differential binding preferences and relative binding affinities of PFCs to ERs of humans and other species, a cross-species comparison is necessary to effectively assess the health risk of PFCs to humans. In the present work, the species-specific binding characterizations between two PFCs, including perfluorooctane sulfonate (PFOS) and PFOS(4m, 5m), and the different ERαs from Rattus norvegicus, rainbow trout, and humans were explored based on a molecular dynamic modeling. The results proved that linear perfluorinated compound PFOS could make a much stronger binding to ERαs than the branched perfluorinated compounds PFOS(4m, 5m). In addition, PFOS and PFOS(4m, 5m) presented species-difference among human, Rattus norvegicus, and rainbow trout. The binding affinity with ERα presented an order of human >Rattus norvegicus > rainbow trout. This suggested that PFOS and PFOS(4m, 5m) have the strongest effects on human ERα over the other two species. As a consequence, the PFCs were more sensitive to human ERα than to those of Rattus norvegicus and rainbow trout. This resulted in greater susceptibility to adverse effects, which suggested a possible underestimation of the endocrine-disrupting effects of PFCs in humans. The cross-species comparison represents the first and necessary step to identify species-specific binding mechanisms and to accurately evaluate the potential health risks of PFCs in humans.

Keywords

Perfluorinated compounds (PFCs) Estrogen receptor α (ERα) Molecular dynamics Species difference 

Notes

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (No. 31000017) (No.21207056), State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences (KF2015-17), Key Laboratory of Chemistry and Quality for Traditional Chinese Medicines of the University of Gansu Province, Gansu University of Chinese Medicines (zzy-2016-01), Fundamental Research Funds for the Central Universities (lzujbky-2017-200; lzujbky-2017-kb05; LZU-JZH1914), Gansu Provincial Administration of traditional Chinese Medicine (GZK-2017-63), and Lanzhou talent innovation and entrepreneurship technology program (2016-RC-19).

Supplementary material

894_2018_3878_MOESM1_ESM.docx (1 mb)
ESM 1 (DOCX 1060 kb)

References

  1. 1.
    Buck RC, Franklin J, Berger U, Conder JM, Cousins IT, de Voogt P, Jensen AA, Kannan K, Mabury SA, van Leeuwen SP (2011) Perfluoroalkyl and polyfluoroalkyl substances in the environment: terminology, classification, and origins. Integr Environ Assess Manag 7(4):513–541CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Cui Y, Liu W, Xie W, Yu W, Wang C, Chen H (2015) Investigation of the effects of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) on apoptosis and cell cycle in a zebrafish (Danio rerio) liver cell line. Int J Environ Res Public Health 12(12):15673–15682CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Stevenson CN, MacManus-Spencer LA, Luckenbach T, Luthy RG, Epel D (2006) New perspectives on perfluorochemical ecotoxicology: inhibition and induction of an efflux transporter in the marine mussel, Mytilus californianus. Environ Sci Technol 40(17):5580–5585CrossRefPubMedGoogle Scholar
  4. 4.
    Giesy JP, Kannan K (2001) Global distribution of perfluorooctane sulfonate in wildlife. Environ Sci Technol 35(7):1339–1342CrossRefPubMedGoogle Scholar
  5. 5.
    Higgins CP, Field JA, Criddle CS, Luthy RG (2005) Quantitative determination of perfluorochemicals in sediments and domestic sludge. Environ Sci Technol 39(11):3946–3956CrossRefPubMedGoogle Scholar
  6. 6.
    Jones PD, Hu W, De Coen W, Newsted JL, Giesy JP (2003) Binding of perfluorinated fatty acids to serum proteins. Environ Toxicol Chem 22(11):2639–2649CrossRefPubMedGoogle Scholar
  7. 7.
    Kudo N, Kawashima Y (2003) Toxicity and toxicokinetics of perfluorooctanoic acid in humans and animals. J Toxicol Sci 28(2):49–57CrossRefPubMedGoogle Scholar
  8. 8.
    Park S, Zenobio JE, Lee LS (2017) Perfluorooctane sulfonate (PFOS) removal with Pd0/nFe0 nanoparticles: adsorption or aqueous Fe-complexation, not transformation? J Hazard Mater 342:20–28CrossRefPubMedGoogle Scholar
  9. 9.
    Conder JM, Hoke RA, De Wolf W, Russell MH, Buck RC (2008) Are PFCAs bioaccumulative? A critical review and comparison with regulatory criteria and persistent lipophilic compounds. Environ Sci Technol 42(4):995–1003CrossRefPubMedGoogle Scholar
  10. 10.
    Lau C, Anitole K, Hodes C, Lai D, Pfahles-Hutchens A, Seed J (2007) Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicol Sci 99(2):366–394CrossRefPubMedGoogle Scholar
  11. 11.
    Crinnion WJ (2010) The CDC fourth national report on human exposure to environmental chemicals: what it tells us about our toxic burden and how it assist environmental medicine physicians. Altern Med Rev 15(2):101–109PubMedGoogle Scholar
  12. 12.
    Burendahl S, Treuter E, Nilsson L (2008) Molecular dynamics simulations of human LRH-1: the impact of ligand binding in a constitutively active nuclear receptor. Biochemistry 47(18):5205–5215CrossRefPubMedGoogle Scholar
  13. 13.
    Nwachukwu JC, Srinivasan S, Zheng Y, Wang S, Min J, Dong C, Liao Z, Nowak J, Wright NJ, Houtman R (2016) Predictive features of ligand-specific signaling through the estrogen receptor. Mol Syst Biol 12(4):864CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Yi P, Wang Z, Feng Q, Pintilie GD, Foulds CE, Lanz RB, Ludtke SJ, Schmid MF, Chiu W, O’Malley BW (2015) Structure of a biologically active estrogen receptor-coactivator complex on DNA. Mol Cell 57(6):1047–1058CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Kjeldsen LS, Bonefeld-Jorgensen EC (2013) Perfluorinated compounds affect the function of sex hormone receptors. Environ Sci Pollut Res Int 20(11):8031–8044CrossRefPubMedGoogle Scholar
  16. 16.
    Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P (1986) Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-a. Nature 320(6058):134–139CrossRefPubMedGoogle Scholar
  17. 17.
    Albrecht PP, Torsell NE, Krishnan P, Ehresman DJ, Frame SR, Chang SC, Butenhoff JL, Kennedy GL, Gonzalez FJ, Peters JM (2013) A species difference in the peroxisome proliferator-activated receptor α-dependent response to the developmental effects of perfluorooctanoic acid. Toxicol Sci 131(2):568–582CrossRefPubMedGoogle Scholar
  18. 18.
    Benninghoff AD, Bisson WH, Koch DC, Ehresman DJ, Kolluri SK, Williams DE (2011) Estrogen-like activity of perfluoroalkyl acids in vivo and interaction with human and rainbow trout estrogen receptors in vitro. Toxicol Sci 120(1):42–58CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Tilton SC, Orner GA, Benninghoff AD, Carpenter HM, Hendricks JD, Pereira CB, Williams DE (2008) Genomic profiling reveals an alternate mechanism for hepatic tumor promotion by perfluorooctanoic acid in rainbow trout. Environ Health Perspect. 116(8):1047–1055CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Benninghoff AD, Orner GA, Buchner CH, Hendricks JD, Duffy AM, Williams DE (2012) Promotion of hepatocarcinogenesis by perfluoroalkyl acids in rainbow trout. Toxicol Sci 125(1):69–78CrossRefPubMedGoogle Scholar
  21. 21.
    da Silva Lima CH, de Alencastro RB, Kaiser CR, de Souza MV, Rodrigues CR, Albuquerque MG (2015) Aqueous molecular dynamics simulations of the M. tuberculosis Enoyl-ACP reductase-NADH system and its complex with a substrate mimic or diphenyl ethers inhibitors. Int J Mol Sci 16(10):23695–23722CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Blair RM, Fang H, Branham WS, Hass BS, Dial SL, Moland CL, Tong W, Shi L, Perkins R, Sheehan DM (2000) The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands. Toxicol Sci 54(1):138–153CrossRefPubMedGoogle Scholar
  23. 23.
    Matthews J, Celius T, Halgren R, Zacharewski T (2000) Differential estrogen receptor binding of estrogenic substances: a species comparison. J Steroid Biochem Mol Biol 74(4):223–234CrossRefPubMedGoogle Scholar
  24. 24.
    Olsen CM, Meussen-Elholm ET, Hongslo JK, Stenersen J, Tollefsen KE (2005) Estrogenic effects of environmental chemicals: an interspecies comparison. Comp Biochem Physiol C Toxicol Pharmacol 141(3):267–274CrossRefPubMedGoogle Scholar
  25. 25.
    Zheng L, Lin VC, Mu Y (2016) Exploring flexibility of progesterone receptor ligand binding domain using molecular dynamics. PLoS One 11(11):e0165824CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Roy A, Kucukural A, Zhang Y (2010) I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc 5(4):725–738CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Guetotettay C, Pestananobles R, Drososramirez JC (2016) Determination of the protonation state for the catalytic dyad in β-secretase when bound to hydroxyethylamine transition state analogue inhibitors: a molecular dynamics simulation study. J Mol Graph Model 66:155CrossRefGoogle Scholar
  28. 28.
    Stetz G, Verkhivker GM (2016) Probing allosteric inhibition mechanisms of the Hsp70 chaperone proteins using molecular dynamics simulations and analysis of the residue interaction networks. J Chem Inf Model 56(8):1490CrossRefPubMedGoogle Scholar
  29. 29.
    Zhou Z, Madrid M, Evanseck JD, Madura JD (2005) Effect of a bound non-nucleoside RT inhibitor on the dynamics of wild-type and mutant HIV-1 reverse transcriptase. J Am Chem Soc 127(49):17253–17260CrossRefPubMedGoogle Scholar
  30. 30.
    Kumari R, Kumar R, Lynn A (2014) g_mmpbsa--a GROMACS tool for high-throughput MM-PBSA calculations. J Chem Inf Model 54(7):1951–1962CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Kaili Qu
    • 1
  • Juanjuan Song
    • 2
  • Yu Zhu
    • 3
  • Yaquan Liu
    • 1
  • Chunyan Zhao
    • 1
  1. 1.School of PharmacyLanzhou UniversityLanzhouChina
  2. 2.Pulmonary Hospital of LanzhouLanzhouChina
  3. 3.Environmental Protection Department of Gansu ProvinceLanzhouChina

Personalised recommendations