In vitro molecular mechanisms of bisphenol A action

Wetherill, Yelena B.; Akingbemi, Benson T.; Kanno, Jun; McLachlan, John A.; Nadal, Ángel; Sonnenschein, Carlos; Watson, Cheryl S.; Zoeller, R. Thomas; Belcher, Scott M.

doi:10.1016/j.reprotox.2007.05.010

Cited by 831 publications

(641 citation statements)

References 170 publications

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“…Rapid modulation of ERK and AKT signaling in response to BPA has been observed in neurons, immune cells, and during brain development (14,(40)(41)(42). As far as we know, no information is available on the involvement of these BPA-induced rapid responses on cancer cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

et al. 2008

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SummaryA wide variety of environmental contaminants exert estrogenic actions in wildlife, laboratory animals, and in human beings through binding to nuclear estrogen receptors (ERs). Here, the mechanism(s) of bisphenol A (BPA) to induce cell proliferation and the occurrence of its bioremediation by treatment with laccase are reported. BPA, highly present in natural world and considered as a model of environmental estrogen action complexity, promotes human cancer cell proliferation via ERa-dependent signal transduction pathways. Similar to 17b-estradiol, BPA increases the phosphorylation of both extracellular regulated kinase and AKT. Specific inhibitors of these kinase completely block the BPA effect on cancer cell proliferation. Notably, high BPA concentrations (i.e., 0.1 and 1 mM) are cytotoxic even in ERa-devoid cancer cells, indicating that an ERa-independent mechanism participates to BPA-induced cytotoxicity. On the other hand, BPA oxidation by laccase impairs the binding of this environmental estrogen to ERa loosing at all ERa-dependent effect on cancer cell proliferation. Moreover, the laccase-catalyzed oxidation of BPA reduces the BPA cytotoxic effect. Thus, laccase appears to impair BPA action(s), representing an invaluable bioremediation enzyme.2008 IUBMB IUBMB Life, 60(12): 843-852, 2008

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Section: Discussionmentioning

confidence: 99%

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

et al. 2008

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“…Examples of low dose effects of BPA have been reported in a wide variety of tissues and cell types (vom Saal & Hughes, 2005;Wetherill et al, 2007), although the mechanism of action to explain them are still unclear. One explanation could be that BPA may act via ER through mechanisms other than binding to ERE.…”

Section: E2 and Bpa Are Equally Effective Through A Non-classical Estmentioning

confidence: 99%

The pancreatic β-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes

Nadal

Alonso-Magdalena

Soriano

et al. 2009

Molecular and Cellular Endocrinology

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. The pancreatic β-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes. Molecular and Cellular Endocrinology, Elsevier, 2009, 304 (1-2) Please cite this article as: Nadal, A., Alonso-Magdalena, P., Soriano, S., Quesada, I., Ropero, A.B., The pancreatic ␤-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes, Molecular and Cellular Endocrinology (2008), doi:10.1016/j.mce.2009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. THE PANCREATIC -CELL AS A TARGET OF ESTROGENS AND XENOESTROGENS: IMPLICATIONS FOR BLOOD GLUCOSE HOMEOSTASIS AND DIABETESAngel Rosen & Spiegelman, 2006;Fritsche et al., 2008). During the fasting state, insulin remains at low levels because plasma glucose concentration is low. In this situation, the levels of the counter-regulatory hormones, glucagon, adrenaline and corticosteroids are increased to promote hepatic glucose production. In contrast, insulin, the only hormone in the body able to decrease blood glucose levels, is increased during the fed state. Insulin decreases blood glucose by promoting adipocyte and muscle glucose uptake, as well as by preventing the liver from producing glucose by suppressing glycogenolysis and gluconeogenesis (Fritsche et al., 2008). neurotransmitters, hormones and nutrients, among which glucose is the most important.Normally, in response to short glucose stimulation, insulin biosynthesis is regulated by the increased translation of the preproinsulin transcript. After a prolonged glucose exposure, however, it is regulated via the insulin gene transcription (Orland et al., 1985;Permutt & Rotwein, 1983;Poitout et al., 2006). Both transcriptional and translational regulation of insulin biosynthesis is essential to maintain the intracellular stores of insulin on a long term basis.The secretory response of -cells depends on their electrical activity. This consists of oscillations of the membrane potential that range from electrically silent periods to depolarised plateaus on which Ca 2+ -action potentials originate (Rorsman et al., 2000).The classical stimulus-secretion coupling that drives insulin release involves the closure of K ATP channels by increasing the intracellular ATP/ADP ratio (Ashcroft et al., 1984) and diadenosine polyphosphates concentration (DPs) (Ripoll et al., 1996) oscillatory pattern is originated (Nadal et al., 1999;Santos et al., 1991;Valdeolmillos et al., 1989), which triggers a pulsatile insulin secretion (Barbosa et al., 1998;Gilon et al., 1993;Dyachok et al., 2008). Estrogens, estrogen receptors and blood glucose homeostasisT...

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“…BPA attracted the attention of regulatory agencies and scientists in dozens of countries because of its estrogenic properties in vitro and in vivo and the conserved role that estrogen plays in regulating human and animal physiology and pathophysiology (Dodds and Lawson 1936;Markey et al 2001;Wetherill et al 2007). Biochemical assays have examined the kinetics of BPA binding to the estrogen receptors (ERs) and have determined that BPA binds both ERα and ERβ, with approximately 10 times higher affinity for ERβ (Gould et al 1998;Kuiper et al 1998).…”

mentioning

confidence: 99%

“…However, results from several studies have revealed that BPA can stimulate rapid cellular responses at very low concentrations, below the levels where BPA is expected to bind to the classical nuclear ERs (Welshons et al 2006). BPA has also been shown to bind to a membrane-associated ER and produce non-genomic steroid actions (Wetherill et al 2007) with the same efficacy and potency as estradiol (Alonso-Magdalena et al 2005;Hugo et al 2008). Whatever the mechanism, BPA can cause effects in animal models at doses in the range of human exposures, indicating that it can act at lower doses than predicted from some in vitro and in vivo assays (Richter et al 2007;Vandenberg et al 2007;vom Saal et al 2007;Wetherill et al 2007).…”

mentioning

confidence: 99%

Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

Vandenberg

Chahoud

Heindel³

et al. 2012

Ciênc. saúde coletiva

331

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Estudos de biomonitoração do sistema urinário, circulatório e tecidos indicam grande exposição ao Bisfenol A Resumo Bisfenol A (BPA) é um dos produtos quí-micos mais produzido em todo o mundo, e a exposição humana a ele é considerada onipresente. Assim, há preocupações de que a quantidade de BPA para o qual os seres humanos estão expostos podem causar efeitos adversos à saúde. Nós examinamos muitas possibilidades sobre o porquê estudos de biomonitorização e toxicocinética podem chegar a conclusões aparentemente conflitantes. Mais de 80 estudos publicados de biomonitorização humana que mediram a concentração de BPA em tecidos humanos, urina, sangue e outros fluidos, juntamente com dois estudos de toxicocinéti-ca do metabolismo humano BPA foram examinados. BPA não conjugado foi detectado no sangue (nonanogramas por mililitro gama), e BPA conjugado foi detectado na grande maioria das amostras de urina. Em contraste, estudos de toxico-cinética propuseram que os seres humanos não são internamente expostos ao BPA. Dados disponíveis de estudos de biomonitorização indicam que a população em geral está exposta ao BPA e em risco de exposição interna ao BPA não conjugado. Os dois estudos de toxicocinética, que sugeriram a exposição humana ao BPA é insignificante, têm deficiências significativas e estão diretamente refutados por outros estudos e, portanto não são confiáveis para fins de avaliação de risco. Palavras-chave Disruptor endócrino, Exposição humana, Modelo PBPK/PBTK, Gravidez, Avaliação de risco, Toxicocinética Abstract Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. We examined many possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. More than 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism were examined. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes.

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In vitro molecular mechanisms of bisphenol A action

Cited by 831 publications

References 170 publications

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

The pancreatic β-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes

Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

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