A transgenic mouse model expressing an ERα folding biosensor reveals the effects of Bisphenol A on estrogen receptor signaling

Sekar, Thillai V.; Foygel, Kira; Massoud, Tarik F.; Gambhir, Sanjiv S.; Paulmurugan, Ramasamy

doi:10.1038/srep34788

Cited by 20 publications

(10 citation statements)

References 46 publications

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“…BPA binds to ERs and exerts estrogen-like effects 26 ; thus, it was reasonable that ERs may be involved in BPA-induced pathological effects. PC-12 cells were pre-incubated with the estrogen receptor ERα/β inhibitor ICI 182780 (30 μM) or the GPR30 inhibitor G15 (30 μM) for 30 min prior to BPA treatment,since both of 30 μM ICI 182780 and G15 did not obviously affect cell viability (Fig.…”

Section: Resultsmentioning

confidence: 99%

Involvement of Insulin Signaling Disturbances in Bisphenol A-Induced Alzheimer’s Disease-like Neurotoxicity

Wang

Xie

et al. 2017

Sci Rep

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Bisphenol A (BPA), a member of the environmental endocrine disruptors (EDCs), has recently received increased attention because of its effects on brain insulin resistance. Available data have indicated that brain insulin resistance may contribute to neurodegenerative diseases. However, the associated mechanisms that underlie BPA-induced brain-related outcomes remain largely unknown. In the present study, we identified significant insulin signaling disturbances in the SH-SY5Y cell line that were mediated by BPA, including the inhibition of physiological p-IR Tyr1355 tyrosine, p-IRS1 tyrosine 896, p-AKT serine 473 and p-GSK3α/β serine 21/9 phosphorylation, as well as the enhancement of IRS1 Ser307 phosphorylation; these effects were clearly attenuated by insulin and rosiglitazone. Intriguingly, Alzheimer’s disease (AD)-associated pathological proteins, such as BACE-1, APP, β-CTF, α-CTF, Aβ 1–42 and phosphorylated tau proteins (S199, S396, T205, S214 and S404), were substantially increased after BPA exposure, and these effects were abrogated by insulin and rosiglitazone treatment; these findings underscore the specific roles of insulin signaling in BPA-mediated AD-like neurotoxicity. Thus, an understanding of the regulation of insulin signaling may provide novel insights into potential therapeutic targets for BPA-mediated AD-like neurotoxicity.

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Section: Resultsmentioning

confidence: 99%

Involvement of Insulin Signaling Disturbances in Bisphenol A-Induced Alzheimer’s Disease-like Neurotoxicity

Wang

Xie

et al. 2017

Sci Rep

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“…BPA and BPS act primarily by binding to ESR1 and ESR2 (Grignard et al 2012;Molina-Molina et al 2013), where they can induce agonistic (Li et al 2018b;Sekar et al 2016) or antagonistic (Molina-Molina et al 2013;Vigezzi et al 2016) effects. While most studies have focused on transcriptional effects induced through nESR binding, increasing evidence indicates that these chemicals can induce rapid effects through binding and activation of mESR.…”

Section: Phenolic Chemicalsmentioning

confidence: 99%

Endocrine disruption through membrane estrogen receptors and novel pathways leading to rapid toxicological and epigenetic effects

Rosenfeld

Cooke

2019

The Journal of Steroid Biochemistry and Molecular Biology

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Estrogen binding to estrogen receptors (ESR) triggers signaling cascades within cells. Historically, a major emphasis has been characterizing estrogen-induced genomic actions resulting from binding to nuclear estrogen receptor 1 (nESR1). However, recent evidence indicates the first receptors estrogens encounter as they enter a cell, membrane ESR1 (mESR1), also play crucial roles. Membrane and nuclear ESR are derived from the same transcripts but the former are directed to the membrane via palmitoylation. Binding and activation of mESR1 leads to rapid fluctuations in cAMP and Ca +2 and stimulation of protein kinase pathways. Endocrine disrupting chemicals (EDC) that mimic 17β-estradiol can signal through mESR1 and elicit non-genomic effects. Most current EDC studies have focused on genomic actions via nESR1. However, increasing number of studies have begun to examine potential EDC effects mediated through mESR1, and some EDC might have higher potency for signaling through mESR1 than nESR1. The notion that such chemicals might also affect mESR1 signaling via palmitoylation and depalmitoylation pathways has also begun to gain currency. Recent development of transgenic mice that lack either mESR1 or nESR1, while retaining functional ESR1 in the other compartment, will allow more precise in vivo approaches to determine EDC effects through nESR1 and/or mESR1. It is increasingly becoming apparent in this quickly evolving field that EDC directly affect mESR and estrogen signaling, but such chemicals can also affect proportion of ESR reaching the membrane.Future E D C studies should be designed to consider the full range of effects through mESR alone and in combination with nESR.

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“…Recently, a GEMM expressing an ERα folding-biosensor has been developed. In these mice it is possible to evaluate the impact of diverse estrogenic ligands and to study the estrogen induced carcinogenesis in vivo ( Sekar et al, 2016 ).…”

Section: Transgenic Reporter Mouse Models For Blimentioning

confidence: 99%

Transgenic Animal Models to Visualize Cancer-Related Cellular Processes by Bioluminescence Imaging

Manni¹,

Latouliere²,

Gurtner³

et al. 2019

Front. Pharmacol.

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Preclinical animal models are valuable tools to improve treatments of malignant diseases, being an intermediate step of experimentation between cell culture and human clinical trials. Among different animal models frequently used in cancer research are mouse and, more recently, zebrafish models. Indeed, most of the cellular pathways are highly conserved between human, mouse and zebrafish, thus rendering these models very attractive. Recently, several transgenic reporter mice and zebrafishes have been generated in which the luciferase reporter gene are placed under the control of a promoter whose activity is strictly related to specific cancer cellular processes. Other mouse models have been generated by the cDNA luciferase knockin in the locus of a gene whose expression/activity has increased in cancer. Using BioLuminescence Imaging (BLI), we have now the opportunity to spatiotemporal visualize cell behaviors, among which proliferation, apoptosis, migration and immune responses, in any body district in living animal in a time frame process. We provide here a review of the available models to visualized cancer and cancer-associated events in living animals by BLI and as they have been successful in identifying new stages of early tumor progression, new interactions between different tissues and new therapeutic responsiveness.

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A transgenic mouse model expressing an ERα folding biosensor reveals the effects of Bisphenol A on estrogen receptor signaling

Cited by 20 publications

References 46 publications

Involvement of Insulin Signaling Disturbances in Bisphenol A-Induced Alzheimer’s Disease-like Neurotoxicity

Involvement of Insulin Signaling Disturbances in Bisphenol A-Induced Alzheimer’s Disease-like Neurotoxicity

Endocrine disruption through membrane estrogen receptors and novel pathways leading to rapid toxicological and epigenetic effects

Transgenic Animal Models to Visualize Cancer-Related Cellular Processes by Bioluminescence Imaging

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