Receptor-binding affinities of bisphenol A and its next-generation analogs for human nuclear receptors

Liu, Xiaohui; Sakai, Hiroki; Nishigori, Mitsuhiro; Suyama, Kyozo; Nawaji, Tasuku; Shin, Ikeda; Nishigouchi, Makoto; Okada, Hiroyuki; Matsushima, Ayami; Nose, Takeru; Shimohigashi, Miki; Shimohigashi, Yasuyuki

doi:10.1016/j.taap.2019.114610

Cited by 44 publications

(22 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This reinforces the conclusion of the Tox21 screen, performed on 8305 compounds, according to which many environmental chemicals do not act as TRα1 ligand at non-toxic concentrations, either as agonists or antagonists(Paul-Friedman et al 2019). This contrasts with other nuclear receptors, for which a number of environmental ligands have been identified(Toporova et al 2020, Liu et al 2019. This peculiarity probably reflects the small size of the ligand binding pocket of TRs, and the specific chemical properties of their natural iodinated ligands, T4 and T3.…”

supporting

confidence: 79%

In vitro assessment of the capacity of pesticides to act as agonists/antagonists of the thyroid hormone nuclear receptors

Zekri

Dall'Agnol

Flamant

et al. 2020

Preprint

View full text Add to dashboard Cite

SummarySeveral in vitro tests, including transcriptome analysis of neural cells, were performed to assess the capacity of 33 pesticides to act as thyroid hormone disruptors (THD). Although some pesticides elicit a cellular response, which interferes with thyroid hormone signaling, we found no evidence that they can act as receptor agonists or antagonists. We conclude that the nuclear receptors of thyroid hormone are not common targets of THD, and that pesticide neurodevelopmental toxicity is not explained by a general alteration of neural cell response to thyroid hormone.

show abstract

supporting

confidence: 79%

In vitro assessment of the capacity of pesticides to act as agonists/antagonists of the thyroid hormone nuclear receptors

Zekri

Dall'Agnol

Flamant

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…This reinforces the conclusion of the Tox21 screen, performed on 8305 compounds, according to which many environmental chemicals do not act as TRα1 ligand at non-toxic concentrations, either as agonists or antagonists ( Paul-Friedman et al., 2019 ). TRα1 differs from other nuclear receptors, for which a number of environmental ligands have been identified ( Liu et al., 2019 ; Toporova and Balaguer, 2020 ). This peculiarity probably reflects the small size of the ligand binding pocket of TRs, and the specific chemical properties of their natural iodinated ligands, T4 and T3.…”

Section: Discussionmentioning

confidence: 99%

In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors

Zekri

Agnol²,

Flamant³

et al. 2021

iScience

View full text Add to dashboard Cite

Summary Chemicals acting as thyroid hormone disruptors (THDs) are of a particular concern for public health, considering the importance of this hormone in neurodevelopment and metabolic processes. They might either alter the circulating level of thyroid hormone (TH) or interfere with the cellular response to the hormonal stimulation. In order to assess this later possibility we selected 39 pesticides and combined several in vitro tests. Reporter assays respectively addressed the transactivation capacity of the full-length TH nuclear receptor TRα1, the transactivation capacity of its C-terminal ligand binding domain, or the ability of the hormone to destabilize the interaction between TRα1 and the transcriptional corepressor NcoR. Although some pesticides elicit a cellular response, which sometimes interferes with TH signaling, RNA-seq analysis provided no evidence that they can act as TRα1 agonists or antagonists. Their neurodevelopmental toxicity in mammals cannot be explained by an alteration of the response to TH.

show abstract

“…In epidemiological studies, BPA has been shown to affect insulin synthesis and release as well as insulin signaling [ 184 ]. In vitro NR binding assays indicated a very high affinity (<20 nM) of several bisphenols such as bisphenol A, AF, B, and C for human CAR [ 185 ], which was similar to their affinity for estrogen receptors ( Table 2 .). In contrast, human PXR bound these bisphenols only at micromolar concentrations.…”

Section: Metabolic Effects Of Edc Classes Potentially Mediated By mentioning

confidence: 98%

Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR

Küblbeck

Niskanen

Honkakoski

2020

Cells

View full text Add to dashboard Cite

During the last two decades, the constitutive androstane receptor (CAR; NR1I3) has emerged as a master activator of drug- and xenobiotic-metabolizing enzymes and transporters that govern the clearance of both exogenous and endogenous small molecules. Recent studies indicate that CAR participates, together with other nuclear receptors (NRs) and transcription factors, in regulation of hepatic glucose and lipid metabolism, hepatocyte communication, proliferation and toxicity, and liver tumor development in rodents. Endocrine-disrupting chemicals (EDCs) constitute a wide range of persistent organic compounds that have been associated with aberrations of hormone-dependent physiological processes. Their adverse health effects include metabolic alterations such as diabetes, obesity, and fatty liver disease in animal models and humans exposed to EDCs. As numerous xenobiotics can activate CAR, its role in EDC-elicited adverse metabolic effects has gained much interest. Here, we review the key features and mechanisms of CAR as a xenobiotic-sensing receptor, species differences and selectivity of CAR ligands, contribution of CAR to regulation hepatic metabolism, and evidence for CAR-dependent EDC action therein.

show abstract

Receptor-binding affinities of bisphenol A and its next-generation analogs for human nuclear receptors

Cited by 44 publications

References 107 publications

In vitro assessment of the capacity of pesticides to act as agonists/antagonists of the thyroid hormone nuclear receptors

In vitro assessment of the capacity of pesticides to act as agonists/antagonists of the thyroid hormone nuclear receptors

In vitro assessment of pesticides capacity to act as agonists/antagonists of the thyroid hormone nuclear receptors

Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR

Contact Info

Product

Resources

About