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

Authors
  • Fay, Marta M1, 2
  • Columbo, Daniella1
  • Cotter, Cecelia3
  • Friend, Chandler3
  • Henry, Shawna3
  • Hoppe, Megan3
  • Karabelas, Paulina3
  • Lamy, Corbyn3
  • Lawell, Miranda3
  • Monteith, Sarah3
  • Noyes, Christina3
  • Salerno, Paige3
  • Wu, Jingyi3
  • Zhang, Hedan Mindy3
  • Anderson, Paul J1, 2
  • Kedersha, Nancy1, 2
  • Ivanov, Pavel4, 2, 5
  • Farny, Natalie G6
  • 1 Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, 02115 USA.
  • 2 Department of Medicine, Harvard Medical School, Boston, MA, 02115 USA.
  • 3 Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, MA, 01609 USA.
  • 4 Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, 02115 USA [email protected] [email protected]
  • 5 Broad Institute of Harvard and MIT, Cambridge, MA, 02142 USA.
  • 6 Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, MA, 01609 USA [email protected] [email protected]
Type
Published Article
Journal
Biology Open
Publisher
The Company of Biologists
Publication Date
Jan 10, 2021
Volume
10
Issue
1
Identifiers
DOI: 10.1242/bio.057539
PMID: 33431410
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. © 2021. Published by The Company of Biologists Ltd.

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