Bisphenol A promotes stress granule assembly and modulates the integrated stress response.
Bisphenol A promotes stress granule assembly and modulates the integrated stress response.
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DOI：
10.1242/bio.057539
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发表时间：
2021-01-10
期刊：
影响因子：
2.4
通讯作者：
Farny NG
中科院分区：
文献类型：
--
作者：
Fay MM;Columbo D;Cotter C;Friend C;Henry S;Hoppe M;Karabelas P;Lamy C;Lawell M;Monteith S;Noyes C;Salerno P;Wu J;Zhang HM;Anderson PJ;Kedersha N;Ivanov P;Farny NG
双酚A（BPA）是聚碳酸酯塑料的普遍存在的前体，在超过92%的美国人的血液和血清中发现。虽然BPA已被证明是一种弱雌激素受体（ER）激动剂，但其对细胞应激的影响尚不清楚。在这里，我们证明了高剂量BPA会导致人类细胞中的应激颗粒（SGs）。一种常见的雌激素衍生物β-雌二醇不触发SG，表明SG诱导的机制不是通过ER途径。我们还测试了其他结构相关的环境污染物，包括常见的BPA替代品BPS和BPF，工业化学品4-壬基苯酚（4-NP）和结构相关的化合物4-EP和4-VP，以及农药2，4-二氯苯氧基乙酸（2，4-D）。来自这些相关化合物的可变结果表明，结构同源性不是化合物引起SG的能力的可靠预测因子。此外，我们证明BPA主要通过PERK途径产生典型的SG。最后，我们表明，慢性暴露于低生理相关剂量的BPA抑制SG组装后，随后的急性应激。有趣的是，这种SG抑制不影响eIF 2 α的磷酸化或翻译抑制，因此将SG的物理组装与翻译控制解偶联。我们的工作确定了BPA除了内分泌干扰之外可能对人类健康产生影响的其他影响。总结：生理学相关剂量的增塑剂BPA抑制应激颗粒的形成，以响应继发性急性应激，表明BPA可能影响人类细胞科普细胞应激的方式。
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. Summary: Physiologically-relevant doses of the plasticizing agent BPA inhibit stress granule formation in response to a secondary acute stress, indicating BPA may affect the way human cells cope with cellular stress.
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影响因子：
7.8
作者：
Buchan, J. Ross;Muhlrad, Denise;Parker, Roy
通讯作者：
Parker, Roy
影响因子：
4.5
作者：
Farny, Natalie G.;Kedersha, Nancy L.;Silver, Pamela A.
通讯作者：
Silver, Pamela A.
影响因子：
10.4
作者：
Calafat AM;Kuklenyik Z;Reidy JA;Caudill SP;Ekong J;Needham LL
通讯作者：
Needham LL
DOI：
10.1016/j.jchromb.2015.02.009
发表时间：
2015-04-01
影响因子：
3
作者：
Asimakopoulos, Alexandros G.;Thomaidis, Nikolaos S.
通讯作者：
Thomaidis, Nikolaos S.
影响因子：
2.8
作者：
Gassman NR
通讯作者：
Gassman NR