Skip to main content
SpringerLink
Log in

Low doses of BPF-induced hypertrophy in cardiomyocytes derived from human embryonic stem cells via disrupting the mitochondrial fission upon the interaction between ERβ and calcineurin A-DRP1 signaling pathway

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

Abstract

Bisphenol F (BPF) is a replacement to bisphenol A, which has been extensively used in industrial manufacturing. Its wide detection in various human samples raises increasing concern on its safety. Currently, whether a low dose of BPF compromises cardiac function is still unknown. This study provides the first evidence that low-dose BPF can induce cardiac hypertrophy by using cardiomyocytes derived from human embryonic stem cells (hES). Non-cytotoxic BPF increased cytosolic Ca 2+ influx ([Ca2+ ]c), which was most remarkable at low dose (7 ng/ml) rather than at higher doses. Significant changes in the morphological parameters of mitochondria and significant decreases in ATP production were induced by 7 ng/ml BPF, representing a classic hypertrophic cardiomyocyte. After eliminating the direct effects on mitochondrial fission-related DRP1 by administration of the DRP1 inhibitor Mdivi-1, we examined the changes in [Ca 2+ ]c levels induced by BPF, which enhanced the calcineurin (Cn) activity and induced the abnormal mitochondrial fission via the CnAβ-DRP1 signaling pathway. BPF triggered excessive Ca 2+ influx by disrupting the L-type Ca 2+channel in cardiomyocytes. The interaction between ERβ and CnAβ cooperatively involved in the BPF-induced Ca 2+ influx, which resulted in the abnormal mitochondrial fission and compromised the cardiac function. Our findings provide a feasible molecular mechanism for explaining low-dose BPF-induced cardiac hypertrophy in vitro, preliminarily suggesting that BPF may not be as safe as assumed in humans.

Graphical abstract

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data availability

The data used in the current study are available from the corresponding author on reasonable request.

References

  • Agarwal S, Yadav A, Tiwari SK, Seth B, Chauhan LK, Khare P, et al. Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation. J Biol Chem. 2016;291:15923–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Awada Z, Nasr R, Akika R, Cahais V, Cuenin C, Zhivagui M, et al. DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11:138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Badding MA, Barraj L, Williams AL, Scrafford C, Reiss R. CLARITY-BPA Core Study: Analysis for non-monotonic dose-responses and biological relevance. Food Chem Toxicol. 2019;131:110554.

    Article  CAS  PubMed  Google Scholar 

  • Belcher SM, Chen Y, Yan S, Wang HS. Rapid estrogen receptor-mediated mechanisms determine the sexually dimorphic sensitivity of ventricular myocytes to 17beta-estradiol and the environmental endocrine disruptor bisphenol A. Endocrinology. 2012;153:712–20.

    Article  CAS  PubMed  Google Scholar 

  • Cheng W, Yang SF, Li XL, Liang F, Zhou R, Wang H, et al. Low doses of BPA induced abnormal mitochondrial fission and hypertrophy in human embryonic stem cell-derived cardiomyocytes via the calcineurin-DRP1 signaling pathway: A comparison between XX and XY cardiomyocytes. Toxicol Appl Pharmacol. 2020;388:114850.

    Article  CAS  PubMed  Google Scholar 

  • Derakhshan A, Shu H, Peeters RP, Kortenkamp A, Lindh CH, Demeneix B, et al. Association of urinary bisphenols and triclosan with thyroid function during early pregnancy. Environ Int. 2019;133:105123.

    Article  CAS  PubMed  Google Scholar 

  • Deutschmann A, Hans M, Meyer R, Haberlein H, Swandulla D. Bisphenol A inhibits voltage-activated Ca(2+) channels in vitro: mechanisms and structural requirements. Mol Pharmacol. 2013;83(2):501–11.

  • Duan Y, Yao Y, Wang B, Han L, Wang L, Sun H, et al. Association of urinary concentrations of bisphenols with type 2 diabetes mellitus: A case-control study. Environ Pollut. 2018;243:1719–26.

    Article  CAS  PubMed  Google Scholar 

  • Eladak S, Grisin T, Moison D, Guerquin MJ, N'Tumba-Byn T, Pozzi-Gaudin S, et al. A new chapter in the bisphenol A story: bisphenol S and bisphenol F are not safe alternatives to this compound. Fertil Steril. 2015;103:11–21.

    Article  CAS  PubMed  Google Scholar 

  • Feng YX, Jiao ZH, Shi JC, Li M, Guo QZ, Shao B. Effects of bisphenol analogues on steroidogenic gene expression and hormone synthesis in H295R cells. Chemosphere. 2016;147:9–19.

    Article  CAS  PubMed  Google Scholar 

  • Gear R, Kendziorski JA, Belcher SM. Effects of bisphenol A on incidence and severity of cardiac lesions in the NCTR-Sprague-Dawley rat: A CLARITY-BPA study. Toxicol Lett. 2017;275:123–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geng L, Wang Z, Cui C, Zhu Y, Shi J, Wang J, et al. Rapid Electrical Stimulation Increased Cardiac Apoptosis Through Disturbance of Calcium Homeostasis and Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Cell Physiol Biochem. 2018;47:1167–80.

    Article  CAS  PubMed  Google Scholar 

  • Gomez AM, Ruiz-Hurtado G, Benitah JP, Dominguez-Rodriguez A. Ca2+ Fluxes Involvement in Gene Expression During Cardiac Hypertrophy. Curr Vasc Pharmacol. 2013;11:497–506.

    Article  CAS  PubMed  Google Scholar 

  • Hasan P, Saotome M, Ikoma T, Iguchi K, Kawasaki H, Iwashita T, et al. Mitochondrial fission protein, dynamin-related protein 1, contributes to the promotion of hypertensive cardiac hypertrophy and fibrosis in Dahl-salt sensitive rats. J Mol Cell Cardiol. 2018;121:103–6.

    Article  CAS  PubMed  Google Scholar 

  • Hasnat M, Yuan Z, Naveed M, Khan A, Raza F, Xu D, et al. Drp1-associated mitochondrial dysfunction and mitochondrial autophagy: a novel mechanism in triptolide-induced hepatotoxicity. Cell Biol Toxicol. 2019;35:267–80.

    Article  CAS  PubMed  Google Scholar 

  • Heckel E, Boselli F, Roth S, Krudewig A, Belting HG, Charvin G, et al. Oscillatory Flow Modulates Mechanosensitive klf2a Expression through trpv4 and trpp2 during Heart Valve Development. Curr Biol. 2015;25:1354–61.

    Article  CAS  PubMed  Google Scholar 

  • Hemmi N, Tohyama S, Nakajima K, Kanazawa H, Suzuki T, Hattori F, et al. A massive suspension culture system with metabolic purification for human pluripotent stem cell-derived cardiomyocytes. Stem Cells Transl Med. 2014;3:1473–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hercog K, Maisanaba S, Filipic M, Sollner-Dolenc M, Kac L, Zegura B. Genotoxic activity of bisphenol A and its analogues bisphenol S, bisphenol F and bisphenol AF and their mixtures in human hepatocellular carcinoma (HepG2) cells. Sci Total Environ. 2019;687:267–76.

    Article  CAS  PubMed  Google Scholar 

  • Jha R., Xu R-H, Xu C. (2015). Efficient Differentiation of Cardiomyocytes from Human Pluripotent Stem Cells with Growth Factors. In: Skuse G, Ferran M (eds) Cardiomyocytes Methods in Molecular Biology 1299.

  • Jiang Y, Wang D, Zhang G, Wang G, Tong J, Chen T. Disruption of cardiogenesis in human embryonic stem cells exposed to trichloroethylene. Environ Toxicol. 2016;31:1372–80.

    Article  CAS  PubMed  Google Scholar 

  • Karrer C, Andreassen M, von Goetz N, Sonnet F, Sakhi AK, Hungerbuhler K, et al. The EuroMix human biomonitoring study: Source-to-dose modeling of cumulative and aggregate exposure for the bisphenols BPA, BPS, and BPF and comparison with measured urinary levels. Environ Int. 2020;136:105397.

    Article  CAS  PubMed  Google Scholar 

  • Kurauchi K, Nishikawa T, Miyahara E, Okamoto Y, Kawano Y. Role of metabolites of cyclophosphamide in cardiotoxicity. BMC Rese Notes. 2017;10:406.

    Article  CAS  Google Scholar 

  • Le Fol V, Ait-Aissa S, Sonavane M, Porcher JM, Balaguer P, Cravedi JP, et al. In vitro and in vivo estrogenic activity of BPA, BPF and BPS in zebrafish-specific assays. Ecotoxicol Environ Saf. 2017;142:150–6.

    Article  PubMed  CAS  Google Scholar 

  • Lee YK, Ng KM, Lai WH, Chan YC, Lau YM, Lian Q, et al. Calcium homeostasis in human induced pluripotent stem cell-derived cardiomyocytes. Stem Cell Rev Rep. 2011;7:976–86.

    Article  CAS  PubMed  Google Scholar 

  • Lei B, Huang Y, Liu Y, Xu J, Sun S, Zhang X, et al. Low-concentration BPF induced cell biological responses by the ERalpha and GPER1-mediated signaling pathways in MCF-7 breast cancer cells. Ecotoxicol Environ Saf. 2018;165:144–52.

    Article  CAS  PubMed  Google Scholar 

  • Leonard AP, Cameron RB, Speiser JL, Wolf BJ, Peterson YK, Schnellmann RG, et al. Quantitative analysis of mitochondrial morphology and membrane potential in living cells using high-content imaging, machine learning, and morphological binning. Biochim Biophys Acta. 2015;1853:348–60.

    Article  CAS  PubMed  Google Scholar 

  • Li J, Bach A, Crawford RB, Phadnis-Moghe AS, Chen W, D'Ingillo S, et al. CLARITY-BPA: Effects of chronic Bisphenol A exposure on the immune system: Part 1 - Quantification of the relative number and proportion of leukocyte populations in the spleen and thymus. Toxicology. 2018;396-397:46–53.

    Article  CAS  PubMed  Google Scholar 

  • Li A, Zhuang T, Shi W, Liang Y, Liao C, Song M, et al. Serum concentration of bisphenol analogues in pregnant women in China. Sci Total Environ. 2020;707:136100.

    Article  CAS  PubMed  Google Scholar 

  • Liang Q, Gao XQ, Chen YM, Hong K, Wang HS. Cellular Mechanism of the Nonmonotonic Dose Response of Bisphenol A in Rat Cardiac Myocytes. Environ Health Perspect. 2014;122:601–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liao C, Kannan K. Widespread occurrence of bisphenol A in paper and paper products: implications for human exposure. Environ Sci Technol. 2011;45:9372–9.

    Article  CAS  PubMed  Google Scholar 

  • Liao C, Shi J, Wang X, Zhu Q, Kannan K. Occurrence and distribution of parabens and bisphenols in sediment from northern Chinese coastal areas. Environ Pollut. 2019;253:759–67.

    Article  CAS  PubMed  Google Scholar 

  • Liesa M, Shirihai OS. Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab. 2013;17:491–506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lind T, Lejonklou MH, Dunder L, Kushnir MM, Ohman-Magi C, Larsson S, et al. Developmental low-dose exposure to bisphenol A induces chronic inflammation, bone marrow fibrosis and reduces bone stiffness in female rat offspring only. Environ Res. 2019;177:108584.

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Sakai H, Nishigori M, Suyama K, Nawaji T, Ikeda S, et al. Receptor-binding affinities of bisphenol A and its next-generation analogs for human nuclear receptors. Toxicol Appl Pharmacol. 2019;377:114610.

    Article  CAS  PubMed  Google Scholar 

  • Luz AL, Tokar EJ. Pluripotent Stem Cells in Developmental Toxicity Testing: A Review of Methodological Advances. Toxicol Sci. 2018;165:31–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mayourian J, Ceholski DK, Gonzalez DM, Cashman TJ, Sahoo S, Hajjar RJ, et al. Physiologic, Pathologic, and Therapeutic Paracrine Modulation of Cardiac Excitation-Contraction Coupling. Circ Res. 2018;122:167–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moon SH, Ban K, Kim C, Kim SS, Byun J, Song MK, et al. Development of a novel two-dimensional directed differentiation system for generation of cardiomyocytes from human pluripotent stem cells. Int J Cardiol. 2013;168:41–52.

    Article  PubMed  Google Scholar 

  • Moreman J, Lee O, Trznadel M, David A, Kudoh T, Tyler CR. Acute Toxicity, Teratogenic, and Estrogenic Effects of Bisphenol A and Its Alternative Replacements Bisphenol S, Bisphenol F, and Bisphenol AF in Zebrafish Embryo-Larvae. Environ Sci Technol. 2017;51:12796–805.

    Article  CAS  PubMed  Google Scholar 

  • Mu X, Huang Y, Li X, Lei Y, Teng M, Li X, et al. Developmental Effects and Estrogenicity of Bisphenol A Alternatives in a Zebrafish Embryo Model. Environ Sci Technol. 2018;52:3222–31.

    Article  CAS  PubMed  Google Scholar 

  • Mu X, Liu J, Yuan L, Yang K, Huang Y, Wang C, et al. The mechanisms underlying the developmental effects of bisphenol F on zebrafish. Sci Total Environ. 2019;687:877–84.

    Article  CAS  PubMed  Google Scholar 

  • Padron-Barthe L, Villalba-Orero M, Gomez-Salinero JM, Acin-Perez R, Cogliati S, Lopez-Olaneta M, et al. Activation of Serine One-Carbon Metabolism by Calcineurin Abeta1 Reduces Myocardial Hypertrophy and Improves Ventricular Function. J Am Coll Cardiol. 2018;71:654–67.

    Article  CAS  PubMed  Google Scholar 

  • Park C, Song H, Choi J, Sim S, Kojima H, Park J, et al. The mixture effects of bisphenol derivatives on estrogen receptor and androgen receptor. Environ Pollut. 2020;260:114036.

    Article  CAS  PubMed  Google Scholar 

  • Parra V, Rothermel BA. Calcineurin signaling in the heart: The importance of time and place. J Mol Cell Cardiol. 2017;103:121–36.

    Article  CAS  PubMed  Google Scholar 

  • Pelch K, Wignall JA, Goldstone AE, Ross PK, Blain RB, Shapiro AJ, et al. A scoping review of the health and toxicological activity of bisphenol A (BPA) structural analogues and functional alternatives. Toxicology. 2019a;424:152235.

    Article  CAS  PubMed  Google Scholar 

  • Pelch KE, Li Y, Perera L, Thayer KA, Korach KS. Characterization of Estrogenic and Androgenic Activities for Bisphenol A-like Chemicals (BPs): In Vitro Estrogen and Androgen Receptors Transcriptional Activation, Gene Regulation, and Binding Profiles. Toxicol Sci. 2019b;172(1):23–37.

    Article  CAS  PubMed Central  Google Scholar 

  • Qiu W, Zhan H, Hu J, Zhang T, Xu H, Wong M, et al. The occurrence, potential toxicity, and toxicity mechanism of bisphenol S, a substitute of bisphenol A: A critical review of recent progress. Ecotoxicol Environ Saf. 2019;173:192–202.

    Article  CAS  PubMed  Google Scholar 

  • Sharp WW, Fang YH, Han M, Zhang HJ, Hong Z, Banathy A, et al. Dynamin-related protein 1 (Drp1)-mediated diastolic dysfunction in myocardial ischemia-reperfusion injury: therapeutic benefits of Drp1 inhibition to reduce mitochondrial fission. FASEB J. 2014;28:316–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shekhar S, Sood S, Showkat S, Lite C, Chandrasekhar A, Vairamani M, et al. Detection of phenolic endocrine disrupting chemicals (EDCs) from maternal blood plasma and amniotic fluid in Indian population. Gen Comp Endocrinol. 2017;241:100–7.

    Article  CAS  PubMed  Google Scholar 

  • Shi MX, Whorton AE, Sekulovski N, MacLean JA, Hayashi K. Prenatal Exposure to Bisphenol A, E, and S Induces Transgenerational Effects on Male Reproductive Functions in Mice. Toxicol Sci. 2019;172:303–15.

    Article  CAS  PubMed  Google Scholar 

  • Sirenko O, Grimm FA, Ryan KR, Iwata Y, Chiu WA, Parham F, et al. In vitro cardiotoxicity assessment of environmental chemicals using an organotypic human induced pluripotent stem cell-derived model. Toxicol Appl Pharmacol. 2017;322:60–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soundararajan A, Prabu P, Mohan V, Gibert Y, Balasubramanyam M. Novel insights of elevated systemic levels of bisphenol-A (BPA) linked to poor glycemic control, accelerated cellular senescence and insulin resistance in patients with type 2 diabetes. Mol Cell Biochem. 2019;458:171–83.

    Article  CAS  PubMed  Google Scholar 

  • Steed E, Faggianelli N, Roth S, Ramspacher C, Concordet JP, Vermot J. klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis. Nat Commun. 2016;7:11646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thayer KA, Taylor KW, Garantziotis S, Schurman SH, Kissling GE, Hunt D, et al. Bisphenol A, Bisphenol S, and 4-Hydroxyphenyl 4-Isoprooxyphenylsulfone (BPSIP) in Urine and Blood of Cashiers. Environ Health Perspect. 2016;124:437–44.

    Article  CAS  PubMed  Google Scholar 

  • Torrealba N, Aranguiz P, Alonso C, Rothermel BA, Lavandero S. Mitochondria in Structural and Functional Cardiac Remodeling. Adv Exp Med Biol. 2017;982:277–306.

    Article  CAS  PubMed  Google Scholar 

  • Tsai CY, Kuo WW, Shibu MA, Lin YM, Liu CN, Chen YH, et al. E2/ER beta inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca2+-calcineurin signaling. PLoS One. 2017;12:e0184153.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ulmer BM, Eschenhagen T. Human pluripotent stem cell-derived cardiomyocytes for studying energy metabolism. Biochim Biophys Acta, Mol Cell Res. 2020;1867:118471.

    Article  CAS  Google Scholar 

  • Valente AJ, Maddalena LA, Robb EL, Moradi F, Stuart JA. A simple ImageJ macro tool for analyzing mitochondrial network morphology in mammalian cell culture. Acta Histochem. 2017;119:315–26.

    Article  CAS  PubMed  Google Scholar 

  • Veiga-Lopez A, Moeller J, Sreedharan R, Singer K, Lumeng C, Ye W, et al. Developmental programming: interaction between prenatal BPA exposure and postnatal adiposity on metabolic variables in female sheep. Am J Physiol-Endocrinol Metab. 2016;310:E238–47.

    Article  PubMed  Google Scholar 

  • Wang Q, Luo C, Lu G, Chen Z. Effect of adenosine monophosphate-activated protein kinase-p53-Kruppel-like factor 2a pathway in hyperglycemia-induced cardiac remodeling in adult zebrafish. J Diabetes Investig. 2020;12(3):320–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu D, Wang X, Sun H. The role of mitochondria in cellular toxicity as a potential drug target. Cell Biol Toxicol. 2018;34:87–91.

    Article  CAS  PubMed  Google Scholar 

  • Yang R, Liu S, Liang X, Yin N, Ruan T, Jiang L, et al. F-53B and PFOS treatments skew human embryonic stem cell in vitro cardiac differentiation towards epicardial cells by partly disrupting the WNT signaling pathway. Environ Pollut. 2020;261:114153.

    Article  CAS  PubMed  Google Scholar 

  • Zhang YF, Ren XM, Li YY, Yao XF, Li CH, Qin ZF, et al. Bisphenol A alternatives bisphenol S and bisphenol F interfere with thyroid hormone signaling pathway in vitro and in vivo. Environ Pollut. 2018;237:1072–9.

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Quan Q, Zhang M, Zhang N, Zhang W, Zhan M, et al. Occurrence of bisphenol A and its alternatives in paired urine and indoor dust from Chinese university students: Implications for human exposure. Chemosphere. 2020;247:125987.

    Article  CAS  PubMed  Google Scholar 

Download references

Code availability

Not applicable

Funding

This work was supported by the Shanghai Science & Technology Development Foundation (1914901200), National key R&D program of China (2018YFC1602405), Research Program of Shanghai Collaborative Innovation Center for Translational Medicine (TM201716), and the Interdisciplinary Program of Shanghai Jiao tong University (YG2021QN03; ZH2018QNA68).

Author information

Author notes

  1. Wei Cheng and Xiaolan Li contributed equally to this work.

Authors and Affiliations

  1. School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China, 200025

    Wei Cheng, Xiaolan Li, Shoufei Yang, Yan Li, Yan Feng & Yan Wang

  2. Center for Single-Cell Omics, School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China, 200025

    Hui Wang

  3. The Ninth People’s Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China, 200011

    Yan Wang

  4. Shanghai Collaborative Innovation Center for Translational Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China, 200025

    Yan Wang

Authors
  1. Wei Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaolan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shoufei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yan Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: Wei Cheng, Yan Wang; Methodology: Hui Wang, Yan Wang; Formal analysis and investigation: Wei Cheng, Xiaolan Li, Shoufei Yang; Writing-original draft preparation: Wei Cheng, Xiaolan Li; Writing-review and editing: Wei Cheng, Xiaolan Li; Funding acquisition: Yan Wang, Yan Li, Wei Cheng; Resources: Hui Wang, Yan Feng; Yan Li; Supervision: Yan Wang.

Corresponding author

Correspondence to Yan Wang.

Ethics declarations

Ethics approval

Not applicable

Consent to participate

Not applicable

Consent for publication

Not applicable

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Graphical headlights

1. Low dose of BPF showed hypertrophy potential in H9-CMs.

2. BPF disrupted Ca2+ influx-mediated CnA-DRP1 signaling.

3. ERβ involved in the mitochondrial fission caused by BPF.

4. ERβ interacted with BPF-disrupted CnA-DRP1 signaling.

Supplementary Information

ESM 1

(DOCX 1675 kb)

ESM 2

(AVI 7578 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cheng, W., Li, X., Yang, S. et al. Low doses of BPF-induced hypertrophy in cardiomyocytes derived from human embryonic stem cells via disrupting the mitochondrial fission upon the interaction between ERβ and calcineurin A-DRP1 signaling pathway. Cell Biol Toxicol 38, 409–426 (2022). https://doi.org/10.1007/s10565-021-09615-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-021-09615-y

Keywords

Search

Navigation