دورية أكاديمية
G protein-coupled estrogen receptor activation by bisphenol-A disrupts the protection from apoptosis conferred by the estrogen receptors ERα and ERβ in pancreatic beta cells
| العنوان: | G protein-coupled estrogen receptor activation by bisphenol-A disrupts the protection from apoptosis conferred by the estrogen receptors ERα and ERβ in pancreatic beta cells |
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| المؤلفون: | Babiloni-Chust, Ignacio, Dos Santos, Reinaldo S., Medina-Gali, Regla M., Perez-Serna, Atenea A., Encinar, José A., Martinez-Pinna, Juan, Gustafsson, Jan-Ake, Marroquí, Laura, Nadal, Ángel |
| المساهمون: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología, Fisiología Neuroendocrina (FINE) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2022 |
| المجموعة: | RUA - Repositorio Institucional de la Universidad de Alicante |
| مصطلحات موضوعية: | Apoptosis, Bisphenol-A, Endocrine disruptors, GPER/GPR30, Heterodimers, 17β-estradiol, Estrogen receptors, Fisiología |
| الوصف: | 17β-estradiol protects pancreatic β-cells from apoptosis via the estrogen receptors ERα, ERβ and GPER. Conversely, the endocrine disruptor bisphenol-A (BPA), which exerts multiple effects in this cell type via the same estrogen receptors, increased basal apoptosis. The molecular-initiated events that trigger these opposite actions have yet to be identified. We demonstrated that combined genetic downregulation and pharmacological blockade of each estrogen receptor increased apoptosis to a different extent. The increase in apoptosis induced by BPA was diminished by the pharmacological blockade or the genetic silencing of GPER, and it was partially reproduced by the GPER agonist G1. BPA and G1-induced apoptosis were abolished upon pharmacological inhibition, silencing of ERα and ERβ, or in dispersed islet cells from ERβ knockout (BERKO) mice. However, the ERα and ERβ agonists PPT and DPN, respectively, had no effect on beta cell viability. To exert their biological actions, ERα and ERβ form homodimers and heterodimers. Molecular dynamics simulations together with proximity ligand assays and coimmunoprecipitation experiments indicated that the interaction of BPA with ERα and ERβ as well as GPER activation by G1 decreased ERαβ heterodimers. We propose that ERαβ heterodimers play an antiapoptotic role in beta cells and that BPA- and G1-induced decreases in ERαβ heterodimers lead to beta cell apoptosis. Unveiling how different estrogenic chemicals affect the crosstalk among estrogen receptors should help to identify diabetogenic endocrine disruptors. ; This work was supported by Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) grants BPU2017-86579-R (AN), PID2020-117294RB-I00 (AN, JM-P), Generalitat Valenciana PROMETEO II/2020/006 (AN) and European Union’s Horizon 2020 research and innovation programme under grant agreement GOLIATH No. 825489 (AN). Author laboratories hold grants from Ministerio de Ciencia e Innovación, Agencia Estatal de ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1016/j.envint.2022.107250Test; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2017-86579-R; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117294RB-I00; info:eu-repo/grantAgreement/EC/H2020/825489; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-096724-B-C21; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117569RA-I00; Environment International. 2022, 164: 107250. https://doi.org/10.1016/j.envint.2022.107250Test; 0160-4120 (Print); 1873-6750 (Online); http://hdl.handle.net/10045/123120Test |
| DOI: | 10.1016/j.envint.2022.107250 |
| الإتاحة: | https://doi.org/10.1016/j.envint.2022.107250Test http://hdl.handle.net/10045/123120Test |
| حقوق: | © 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0Test/). ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.D0133ADC |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.envint.2022.107250 |
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