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4 results on '"Le Maire, Albane"'

1. Nuclear receptor profiling of bisphenol-a and its halogenated analogues

Author

Delfosse, Vanessa, Grimaldi, Marina, Le Maire, Albane, Bourguet, William, Balaguer, Patrick, Centre de Biochimie Structurale [Montpellier] (CBS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), This work was supported by Programme National de Recherche sur les Perturbateurs Endocriniens (P.B.), Agence Nationale de Recherches Contaminants, Ecosystèmes, Santé Project 'BISCOT' 2010 Contaminants et Environnements: Métrologie, Santé, Adaptabilité, Comportements et Usages 004 02 (to P.B. and W.B.) and Programme Environnement Cancer Project 'SynerPXR' 2012 (to P.B. and W.B.)., and CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)

Subjects
endocrine disruptor, endocrine system, bisphenol-A, halogenated bisphenol-A, nuclear hormone receptor, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, hormones, hormone substitutes, and hormone antagonists
Abstract

International audience; Bisphenol-A (BPA) is one of the highest-volume chemicals produced worldwide and the widespread exposure of individuals to BPA is suspected to affect a variety of physiological functions, including reproduction, development, and metabolism. Its estrogenic activity has been well documented in the last 15 years. In addition to estrogen receptors, BPA has been also shown to bind to and activate the estrogen-related receptor γ and pregnane X receptor and inhibit the androgen receptor. Halogenated BPAs were also shown to activate the peroxisome proliferator-activated receptor γ and inhibit thyroid hormone receptors. In this chapter, we review recent studies shedding light on the structural and molecular mechanisms by which BPA and its halogenated derivatives interfere with nuclear hormone receptor signaling. These data provide guidelines for the development of safer substitutes devoid of hormonal activity and may help environmental risk assessment.

Published
2014

2. Structural and mechanistic insights into bisphenols action provide guidelines for risk assessment and discovery of bisphenol A substitutes.

Author

Delfosse, Vanessa, Grimaldi, Marina, Pons, Jean-Luc, Boulahtouf, Abdelhay, le Maire, Albane, Cavailles, Vincent, Labesse, Gilles, Bourguet, William, and Balaguer, Patrick

Subjects
BISPHENOL A, ENDOCRINE disruptors, ESTROGEN, PROTEIN structure, C-terminal binding proteins, CRYSTAL structure, NUCLEAR receptors (Biochemistry)
Abstract

Bisphenol A (BPA) is an industrial compound and a well known endocrine-disrupting chemical with estrogenic activity. The wide-spread exposure of individuals to BPA is suspected to affect a variety of physiological functions, including reproduction, development, and metabolism. Here we report that the mechanisms by which BPA and two congeners, bisphenol AF and bisphenol C (BPC), bind to and activate estrogen receptors (ER) α and β differ from that used by 17β-estradiol. We show that bisphenols act as partial agonists of ERs by activating the N-terminal activation function 1 regardless of their effect on the C-terminal activation function 2, which ranges from weak agonism (with BPA) to antagonism (with BPC). Crystallographic analysis of the interaction between bisphenols and ERs reveals two discrete binding modes, reflecting the different activities of compounds on ERs. BPA and 17β-estradiol bind to ERs in a similar fashion, whereas, with a phenol ring pointing toward the activation helix H12, the orientation of BPC accounts for the marked antagonist character of this compound. Based on structural data, we developed a protocol for in silico evaluation of the interaction between bisphenols and ERs or other members of the nuclear hormone receptor family, such as estrogen-related receptor γ and androgen receptor, which are two known main targets of bisphenols. Overall, this study provides a wealth of tools and information that could be used for the development of BPA substitutes devoid of nuclear hormone receptor-mediated activity and more generally for environmental risk assessment. [ABSTRACT FROM AUTHOR]

Published
2012
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3. Peroxisome Proliferator-Activated Receptor ã Is a Target for Halogenated Analogs of Bisphenol A.

Author

Riu, Anne, Grimaldi, Marina, le Maire, Albane, Bey, Gilbert, Phillips, Kevinps, Boulahtouf, Abdelhay, Perdu, Elisabeth, Zalko, Daniel, Bourguet, William, and Balaguer, Patrick

Abstract

Background: The occurrence of halogenated analogs of the xenoestrogen bisphenol A (BPA) has been recently demonstrated both in environmental and human samples. These analogs include brominated [e.g., tetrabromobisphenol A (TBBPA)] and chlorinated [e.g., tetrachlorobisphenol A (TCBPA)] bisphenols, which are both flame retardants. Because of their structural homology with BPA, such chemicals are candidate endocrine disruptors. However, their possible target(s) within the nuclear hormone receptor superfamily has remained unknown. Objectives: We investigated whether BPA and its halogenated analogs could be ligands of estrogen receptors (ERs) and peroxisome proliferator-activated receptors (PPARs) and act as endocrine-disrupting chemicals. Methods: We studied the activity of compounds using reporter cell lines expressing ERs and PPARs. We measured the binding affinities to PPARγ by competitive binding assays with [3H] rosiglitazone and investigated the impact of TBBPA and TCBPA on adipocyte differentiation using NIH3T3-L1 cells. Finally, we determined the binding mode of halogenated BPAs to PPARγ by X-ray crystallography. Results: We observed that TBBPA and TCBPA are human, zebrafish, and Xenopus PPARγ ligands and determined the mechanism by which these chemicals bind to and activate PPARγ. We also found evidence that activation of ERα, ERβ, and PPARγ depends on the degree of halogenation in BPA analogs. We observed that the bulkier brominated BPA analogs, the greater their capability to activate PPARγ and the weaker their estrogenic potential. Conclusions: Our results strongly suggest that polyhalogenated bisphenols could function as obesogens by acting as agonists to disrupt physiological functions regulated by human or animal PPARγ. [ABSTRACT FROM AUTHOR]

Published
2011
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4. Warm Reception? Halogenated BPA Flame Retardants and PPARγ Activation

Author

Kevin J. Phillips, Abdelhay Boulahtouf, William Bourguet, Elisabeth Perdu, Anne Riu, Gilbert Bey, Marina Grimaldi, Daniel Zalko, Patrick Balaguer, Albane le Maire, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), NovAliX, Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Centre de Biochimie Structurale [Montpellier] (CBS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Union FOOD-CT-2003-506319, Agence Nationale de Securite Sanitaire RD-2005-02, Programme National de Recherche sur les Perturbateurs Endocriniens, ECOPI 189, Agence Nationale de la Recherche, Contaminants, Ecosystemes, Sante BISCOT 2010 CESA 004 02, CONTREPERF 2010 CESA 008 03, KISMET 2008 CESA 008 01, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Riu, Anne, Grimaldi, Marina, le Maire, Albane, Bey, Gilbert, Boulahtouf, Abdelhay, Perdu, Elisabeth, Zalko, Daniel, Bourguet, William, and Balaguer, Patrick

Subjects
obesity, PPARγ, Health, Toxicology and Mutagenesis, Xenopus, [SDV]Life Sciences [q-bio], Peroxisome proliferator-activated receptor, BPA, endocrine disruptor, obesity, PPARγ, TBBPA, TCBPA, 010501 environmental sciences, Endocrine Disruptors, Crystallography, X-Ray, Ligands, 01 natural sciences, chemistry.chemical_compound, TCBPA, PPAR delta, Receptor, News | Science Selections, Zebrafish, Flame Retardants, chemistry.chemical_classification, endocrine disruptor, 0303 health sciences, BPA, TBBPA, Xenoestrogen, Reproductive Health, Endocrine disruptor, Biochemistry, Tetrabromobisphenol A, Peroxisome proliferator-activated receptor delta, Bisphenol A (BPA), hormones, hormone substitutes, and hormone antagonists, Chlorophenols, medicine.medical_specialty, endocrine system, Polybrominated Biphenyls, Binding, Competitive, Cell Line, 03 medical and health sciences, Internal medicine, medicine, Animals, Estrogen Receptor beta, Humans, PPAR alpha, Estrogens, Non-Steroidal, 030304 developmental biology, 0105 earth and related environmental sciences, Endocrine Health, urogenital system, Research, Public Health, Environmental and Occupational Health, Estrogen Receptor alpha, PPAR gamma, Endocrinology, Metabolism, chemistry, Nuclear receptor, Estrogen receptor alpha
Abstract

International audience; Background: The occurrence of halogenated analogs of the xenoestrogen bisphenol A (BPA) has been recently demonstrated both in environmental and human samples. These analogs include brominated [e.g., tetrabromobisphenol A (TBBPA)] and chlorinated [e.g., tetrachlorobisphenol A (TCBPA)] bisphenols, which are both flame retardants. Because of their structural homology with BPA, such chemicals are candidate endocrine disruptors. However, their possible target(s) within the nuclear hormone receptor superfamily has remained unknown.Objectives: We investigated whether BPA and its halogenated analogs could be ligands of estrogen receptors (ERs) and peroxisome proliferator–activated receptors (PPARs) and act as endocrine-disrupting chemicals.Methods: We studied the activity of compounds using reporter cell lines expressing ERs and PPARs. We measured the binding affinities to PPARγ by competitive binding assays with [3H]‑rosiglitazone and investigated the impact of TBBPA and TCBPA on adipocyte differentiation using NIH3T3-L1 cells. Finally, we determined the binding mode of halogenated BPAs to PPARγ by X‑ray crystallography.Results: We observed that TBBPA and TCBPA are human, zebrafish, and Xenopus PPARγ ligands and determined the mechanism by which these chemicals bind to and activate PPARγ. We also found evidence that activation of ERα, ERβ, and PPARγ depends on the degree of halogenation in BPA analogs. We observed that the bulkier brominated BPA analogs, the greater their capability to activate PPARγ and the weaker their estrogenic potential.Conclusions: Our results strongly suggest that polyhalogenated bisphenols could function as obesogens by acting as agonists to disrupt physiological functions regulated by human or animal PPARγ.

Published
2011

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