Phytoestrogens and Mycoestrogens Induce Signature Structure Dynamics Changes on Estrogen Receptor α

Abstract

Endocrine disrupters include a broad spectrum of chemicals such as industrial chemicals, natural estrogens and androgens, synthetic estrogens and androgens. Phytoestrogens are widely present in diet and food supplements; mycoestrogens are frequently found in grains. As human beings and animals are commonly exposed to phytoestrogens and mycoestrogens in diet and environment, it is important to understand the potential beneficial or hazardous effects of estrogenic compounds. Many bioassays have been established to study the binding of estrogenic compounds with estrogen receptor (ER) and provided rich data in the literature. However, limited assays can offer structure information with regard to the ligand/ER complex. Our current study surveys the global structure dynamics changes for ERα ligand binding domain (LBD) when phytoestrogens and mycoestrogens bind. The assay is based on the structure dynamics information probed by hydrogen deuterium exchange mass spectrometry and offers a unique viewpoint to elucidate the mechanism how phytoestrogens and mycoestrogens interact with estrogen receptor. The cluster analysis based on the hydrogen deuterium exchange (HDX) assay data reveals a unique pattern when phytoestrogens and mycoestrogens bind with ERα LBD compared to that of estradiol and synthetic estrogen modulators. Our study highlights that structure dynamics could play an important role in the structure function relationship when endocrine disrupters interact with estrogen receptors.

The Cell-Free Expression of MiR200 Family Members Correlates with Estrogen Sensitivity in Human Epithelial Ovarian Cells

“…On the other hand, ERβ is considered to have an antiproliferative effect and shows overexpression in normal tissues [ 16 , 17 , 18 ]. It is important to mention that both BPA and ZEA are able to interact with ERα according to previous studies [ 9 , 19 ]. Estrogen action is also mediated through ER-independent pathways (e.g., by G-protein coupled ERs) and the significance of epigenetic regulatory mechanisms has also been confirmed recently [ 15 ].…”

The Osteogenic Differentiation of Mice Bone Marrow Mesenchymal Stem Cells with Fisetin Phytoestrogen

“…It was known that phytoestrogens simulates estrogen effects, also, it was reported that they have beneficial effects on the bone health and bone regeneration (Lagari et al, 2013). Fisetin is a kind of phytoestrogen (Chen et al, 2016). BMSCs are multipotent stromal cells that can differentiate into mesenchymal cell lineages, such as; osteogenic, adipogenic, myogenic and chondrogenic lineages, many studies have been done on the use of mesenchymal stem cells for bone formation (Guihard et al, 2012).…”

Fisetin attenuates doxorubicin‐induced cardiotoxicity by inhibiting the insulin‐like growth factor II receptor apoptotic pathway through estrogen receptor‐α/‐β activation

“…Fisetin (3,3′,4′,7‐tetrahydroxyflavone) is a flavonoid phytoestrogen found in fruits and vegetables at 2–160 μg/g (Lall et al, 2016). Fisetin has been shown to have anti‐cancer, anti‐coagulatory, and anti‐inflammatory properties (Chen et al, 2016; Long et al, 2020). It also protects against oxidative stress‐related disorders such as diabetes and cardiovascular disease (CVD) (Li et al, 2022).…”

“…Fisetin has been shown to have anti-cancer, anti-coagulatory, and anti-inflammatory properties (Chen et al, 2016;Long et al, 2020). It also protects against oxidative stress-related disorders such as diabetes and cardiovascular disease (CVD) (Li et al, 2022).…”