Direct inhibition of bisphenols on human and rat 11β-hydroxysteroid dehydrogenase 2: Structure-activity relationship and docking analysis

Zhang, Bingru; Tang, Yunbing; Hu, Zhiyan; Shi, Lei; Lu, Jialin; Li, Huitao; Wang, Yiyan; Zhu, Yang; Lin, Han Chieh; Ge, Ren‐Shan

doi:10.1016/j.ecoenv.2023.114715

Cited by 9 publications

(8 citation statements)

References 35 publications

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“…Although excess GC exposure can modulate fetus growth and development, little is known about how the GC system is vulnerable to BPs exposure, particularly during pregnancy. Data suggest that BPs significantly inhibited HSD11β2 activity in humans and rats, possibly by steroid binding site, as evidenced by docking analysis ( 176 ). It is well established that BPA exposure modulates cellular function by their estrogen agonist or androgen antagonist function.…”

Section: Endocrine-disrupting Chemicals Induce Endocrine Dysfunction ...mentioning

confidence: 99%

Modulation of fetoplacental growth, development and reproductive function by endocrine disrupters

Basak,

Varma,

Duttaroy

2023

Front. Endocrinol.

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Maternal endocrine homeostasis is vital to a successful pregnancy, regulated by several hormones such as human chorionic gonadotropin, estrogen, leptin, glucocorticoid, insulin, prostaglandin, and others. Endocrine stress during pregnancy can modulate nutrient availability from mother to fetus, alter fetoplacental growth and reproductive functions. Endocrine disrupters such as bisphenols (BPs) and phthalates are exposed in our daily life's highest volume. Therefore, they are extensively scrutinized for their effects on metabolism, steroidogenesis, insulin signaling, and inflammation involving obesity, diabetes, and the reproductive system. BPs have their structural similarity to 17-β estradiol and their ability to bind as an agonist or antagonist to estrogen receptors to elicit an adverse response to the function of the endocrine and reproductive system. While adults can negate the adverse effects of these endocrine-disrupting chemicals (EDCs), fetuses do not equip themselves with enzymatic machinery to catabolize their conjugates. Therefore, EDC exposure makes the fetoplacental developmental window vulnerable to programming in utero. On the one hand prenatal BPs and phthalates exposure can impair the structure and function of the ovary and uterus, resulting in placental vascular defects, inappropriate placental expression of angiogenic growth factors due to altered hypothalamic response, expression of nutrient transporters, and epigenetic changes associated with maternal endocrine stress. On the other, their exposure during pregnancy can affect the offspring's metabolic, endocrine and reproductive functions by altering fetoplacental programming. This review highlights the latest development in maternal metabolic and endocrine modulations from exposure to estrogenic mimic chemicals on subcellular and transgenerational changes in placental development and its effects on fetal growth, size, and metabolic & reproductive functions.

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Section: Endocrine-disrupting Chemicals Induce Endocrine Dysfunction ...mentioning

confidence: 99%

Modulation of fetoplacental growth, development and reproductive function by endocrine disrupters

Basak,

Varma,

Duttaroy

2023

Front. Endocrinol.

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“…Regarding the mode of action of this EDC, it can bind mainly to estrogen-activated receptors (ER), α and β (ERα and ERβ) and GPR30 receptors (Cimmino et al 2020 ), and thanks to its chemical structure, BPA interacts as an antagonist or agonist, via a receptor-dependent signalling pathway. This EDC can also interact with other receptors, such as the androgen receptor (AR), estrogen-related receptor gamma (ERRγ), thyroid hormone receptor (THR), glucocorticoid receptor (GR) (Prasanth et al 2010 ; Zhang et al 2023 ), progesterone receptor (PR) (Huang et al 2022a ) and PPAR-γ (Acconcia et al 2015 ; Di Pietro et al 2020 ; Rubin 2011 ; Santoro et al 2019 ). Still, the chemical structure of BPA may be an advantage, because BPA cannot adequately reach the boundaries of the hormone-binding site, only inducing a shift of α-helices forming the ligand-binding domain (LBD) (Acconcia et al 2015 ).…”

Section: Exposure To Bpamentioning

confidence: 99%

Effect of bisphenol A on the neurological system: a review update

Costa,

Cairrao

2023

Arch Toxicol

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Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) and one of the most produced synthetic compounds worldwide. BPA can be found in epoxy resins and polycarbonate plastics, which are frequently used in food storage and baby bottles. However, BPA can bind mainly to estrogen receptors, interfering with various neurologic functions, its use is a topic of significant concern. Nonetheless, the neurotoxicity of BPA has not been fully understood despite numerous investigations on its disruptive effects. Therefore, this review aims to highlight the most recent studies on the implications of BPA on the neurologic system. Our findings suggest that BPA exposure impairs various structural and molecular brain changes, promoting oxidative stress, changing expression levels of several crucial genes and proteins, destructive effects on neurotransmitters, excitotoxicity and neuroinflammation, damaged blood–brain barrier function, neuronal damage, apoptosis effects, disruption of intracellular Ca2+ homeostasis, increase in reactive oxygen species, promoted apoptosis and intracellular lactate dehydrogenase release, a decrease of axon length, microglial DNA damage, astrogliosis, and significantly reduced myelination. Moreover, BPA exposure increases the risk of developing neurologic diseases, including neurovascular (e.g. stroke) and neurodegenerative (e.g. Alzheimer’s and Parkinson’s) diseases. Furthermore, epidemiological studies showed that the adverse effects of BPA on neurodevelopment in children contributed to the emergence of serious neurological diseases like attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), depression, emotional problems, anxiety, and cognitive disorders. In summary, BPA exposure compromises human health, promoting the development and progression of neurologic disorders. More research is required to fully understand how BPA-induced neurotoxicity affects human health.

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“…Bilirubin possessed an electron-rich surface that created van der Waals, stacking, and charge transfer interactions with tryptophan [43]. Bisphenols affected the activity of 11β-Hydroxysteroid dehydrogenase 2 by binding to the steroidbinding site and interacting with the catalytic residue tyrosine232 [48]. CD spectrum is widely used to evaluate the secondary structure, folding, and binding properties of proteins since different structural elements have unique CD spectra at a particular wavelength [49].…”

Section: Analysis Of the Binding Of Enzymes And Bilirubinmentioning

confidence: 99%

The Impact of Bilirubin on 7α- and 7β- Hydroxysteroid Dehydrogenases: Spectra and Docking Analysis

Ji¹,

Chen²,

Zhu³

et al. 2023

Preprint

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7α- and 7β-hydroxysteroid dehydrogenases (HSDH) are a pair of enzymes that can catalyze the isomerization of hydroxyl group at site 7 of bile acids. In previous study, we found that the activities of 7α- and 7β-HSDH can be inhibited by bilirubin. In order to clarify the impact, the effects of bilirubin on enzymes were studied by kinetics, spectrum and docking analysis. Relative activity of 7α-HSDH remained less than 40 % under 1 mM bilirubin, for 7β-HSDH, only 18 % activity left at the same condition. Using taurochenodeoxycholic acid (TCDCA) as substrate, the Km of 7α-HSDH was up to 0.63 mM from 0.24 mM after binding with bilirubin, the Km of 7β-HSDH rose from 1.14 mM to 1.87 mM for the catalysis of tauroursodeoxycholic acid (TUDCA). The affinity of 7α- and 7β-HSDH to substrate decreased with the effect of bilirubin. The binding of bilirubin with 7α- or 7β-HSDH were analyzed by UV–Vis spectra, Fluorescence spectra and Circular dichroism (CD) spectra. The results reflected that bilirubin caused a slight change in the secondary structure of 7α- or 7β-HSDH, and the changes were correlated with the ratio of bilirubin to enzyme. 10 candidate molecular docking results were presented to reflect the binding of bilirubin with 7α- or 7β-HSDH and to explore the inhibition mechanism. This research not only provides the more in-depth understanding of 7α- and 7β-HSDH, but also reminds us to avoid the inhibition of bilirubin on hydroxysteroid dehydrogenases.

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Direct inhibition of bisphenols on human and rat 11β-hydroxysteroid dehydrogenase 2: Structure-activity relationship and docking analysis

Cited by 9 publications

References 35 publications

Modulation of fetoplacental growth, development and reproductive function by endocrine disrupters

Modulation of fetoplacental growth, development and reproductive function by endocrine disrupters

Effect of bisphenol A on the neurological system: a review update

The Impact of Bilirubin on 7α- and 7β- Hydroxysteroid Dehydrogenases: Spectra and Docking Analysis

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