Bisphenol A promotes stress granule assembly and modulates the integrated stress response

Bisphenol A promotes stress granule assembly and modulates the integrated stress response

Bisphenol-A (BPA) is a ubiquitous precursor of polycarbonate plastics that is found in the blood and serum of >92% of Americans. While BPA has been well documented to act as a weak estrogen receptor (ER) agonist, its effects on cellular stress are unclear. Here, we demonstrate that high-dose BPA...

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Bibliographic Details
Published in:Biology open Vol. 10; no. 1
Main Authors: Fay, Marta M, Columbo, Daniella, Cotter, Cecelia, Friend, Chandler, Henry, Shawna, Hoppe, Megan, Karabelas, Paulina, Lamy, Corbyn, Lawell, Miranda, Monteith, Sarah, Noyes, Christina, Salerno, Paige, Wu, Jingyi, Zhang, Hedan Mindy, Anderson, Paul J, Kedersha, Nancy, Ivanov, Pavel, Farny, Natalie G
Format: Journal Article
Language:English
Published: England The Company of Biologists Ltd 01-01-2021
The Company of Biologists
Subjects:
17β-Estradiol
2,4-D
Animals
Assembly
Benzhydryl Compounds - metabolism
Benzhydryl Compounds - pharmacology
Bisphenol A
Cell Line
Cellular stress response
Chronic exposure
Contaminants
Dichlorophenoxyacetic acid
eIF-2 Kinase - metabolism
Endocrine disruptors
Estrogen receptors
Estrogens
Eukaryotic Initiation Factor-2 - metabolism
Gene Expression Regulation
Granular materials
Granule cells
Homology
integrated stress response
Mice
Nonylphenol
Pesticides
Phenols - metabolism
Phenols - pharmacology
Phosphorylation
Polycarbonate
Sex hormones
stress granules
Stress Granules - metabolism
Stress, Physiological
translational control
Bisphenol-A
Integrated stress response
Stress granules
Translational control
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Summary:Bisphenol-A (BPA) is a ubiquitous precursor of polycarbonate plastics that is found in the blood and serum of >92% of Americans. While BPA has been well documented to act as a weak estrogen receptor (ER) agonist, its effects on cellular stress are unclear. Here, we demonstrate that high-dose BPA causes stress granules (SGs) in human cells. A common estrogen derivative, β-estradiol, does not trigger SGs, indicating the mechanism of SG induction is not via the ER pathway. We also tested other structurally related environmental contaminants including the common BPA substitutes BPS and BPF, the industrial chemical 4-nonylphenol (4-NP) and structurally related compounds 4-EP and 4-VP, as well as the pesticide 2,4-dichlorophenoxyacetic acid (2,4-D). The variable results from these related compounds suggest that structural homology is not a reliable predictor of the capacity of a compound to cause SGs. Also, we demonstrate that BPA acts primarily through the PERK pathway to generate canonical SGs. Finally, we show that chronic exposure to a low physiologically relevant dose of BPA suppresses SG assembly upon subsequent acute stress. Interestingly, this SG inhibition does not affect phosphorylation of eIF2α or translation inhibition, thus uncoupling the physical assembly of SGs from translational control. Our work identifies additional effects of BPA beyond endocrine disruption that may have consequences for human health.
Bibliography:Present address: Recursion Pharmaceuticals, Salt Lake City, UT, USA.
ISSN:2046-6390
2046-6390
DOI:10.1242/bio.057539