Two persistent organic pollutants which act through different xenosensors (alpha-endosulfan and 2,3,7,8 tetrachlorodibenzo-p-dioxin) interact in a mixture and downregulate multiple genes involved in human hepatocyte lipid and glucose metabolism
| العنوان: | Two persistent organic pollutants which act through different xenosensors (alpha-endosulfan and 2,3,7,8 tetrachlorodibenzo-p-dioxin) interact in a mixture and downregulate multiple genes involved in human hepatocyte lipid and glucose metabolism |
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| المؤلفون: | Sébastien Jacques, Nicolas Cagnard, Franck Letourneur, Martine Aggerbeck, Robert Barouki, Christiane Guguen-Guillouzo, Alix F. Leblanc, Ariane Ambolet-Camoit, Min Ji Kim, Chris Ottolenghi |
| المساهمون: | Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), This work was supported by ANR (Agence Nationale pour la Recherche) [06SETS26, Oncopop], Association de la Recherche sur le Cancer [ARC-3927], INSERM (Institut National de la Santé et de la Recherche Médicale), Université Paris Descartes, MESR (Ministère de l’Enseignement Supérieur et de la Recherche) (doctoral fellowships, Ariane Ambolet-Camoit, Alix Leblanc), and the European Union's Seventh Programme for research, technological development and demonstration (HEALS project, grant agreement Number. 603946)., ANR-06-SEST-0026,ONCOPOP,Polluants Organiques persistants (POP)_ Migration cellulaire et progression tumorale(2006), Toxicologie, Pharmacologie et Signalisation Cellulaire ( U1124 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), ANR-06-SEST-0026,ONCOPOP,Polluants Organiques persistants (POP)_ Migration cellulaire et progression tumorale ( 2006 ), Jonchère, Laurent, Programme Santé-Environnement et Santé-Travail (SEST) - Polluants Organiques persistants (POP)_ Migration cellulaire et progression tumorale - - ONCOPOP2006 - ANR-06-SEST-0026 - SEST - VALID, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) |
| المصدر: | Biochimie Biochimie, Elsevier, 2015, 116, pp.79-91. ⟨10.1016/j.biochi.2015.07.003⟩ Biochimie, Elsevier, 2015, 116, pp.79-91. 〈10.1016/j.biochi.2015.07.003〉 Biochimie, 2015, 116, pp.79-91. ⟨10.1016/j.biochi.2015.07.003⟩ |
| بيانات النشر: | HAL CCSD, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Polychlorinated Dibenzodioxins, genetic structures, medicine.drug_class, [SDV]Life Sciences [q-bio], Blotting, Western, Biology, Retinoid X receptor, Biochemistry, Cell Line, chemistry.chemical_compound, Gene expression, medicine, Humans, Retinoid, Pesticides, Gene, [ SDV ] Life Sciences [q-bio], General Medicine, Metabolism, dioxin, Lipid Metabolism, [SDV] Life Sciences [q-bio], mixture, Metabolic pathway, medicine.anatomical_structure, Glucose, chemistry, 13. Climate action, Hepatocyte, Hepatocytes, HepaRG, Xenobiotic, metabolism, microarray, Endosulfan |
| الوصف: | Individuals, typically, are exposed to mixtures of environmental xenobiotics affecting multiple organs and acting through different xenosensors and pathways in species and cell-type specific manners. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and α-endosulfan are Persistent Organic Pollutants (POPs) and endocrine disruptors which act through different xenosensors and accumulate in the liver. Our objective in this HEALS study was to investigate the effects of the mixture of these POPs on gene expression in a human-derived hepatocyte cell line, HepaRG. We found that, in spite of having largely uncorrelated effects, TCDD and α-endosulfan, when mixed, alter the expression of genes. The combined effects of the mixture of the POPs significantly altered the expression of 100 genes (42 up- and 58 down-regulated) whereas the same concentration of either POP alone did not alter significantly the expression of these genes. For 32 other genes, selective inhibitory crosstalk between TCDD and α-endosulfan was observed. One of the POPs inhibited the effect, on gene expression, of the other in the mixture although, when used alone, that POP did not affect expression. The expression of another 82 genes was significantly altered (up- or down-regulated) by a single POP. The addition of the second POP either increased, in the same direction, the effect on gene expression or had no further effect. At low concentrations (0.2 nM TCDD and 1 μM α-endosulfan), the POPs still had significant effects and the levels of expression of the corresponding proteins were found to be affected for some genes. Particularly striking was the 80-90% inhibition, by the mixture, of the expression of a number of genes of several hepatic intermediary metabolic pathways (glycerolipid metabolism, FXR/RXR activation, glycolysis/gluconeogenesis, retinoid and bile acid biosynthesis), whereas each pollutant alone had only a moderate effect. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0300-9084 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::327927f2e318b36aeba5100c7f133248 https://hal-univ-rennes1.archives-ouvertes.fr/hal-01174215 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....327927f2e318b36aeba5100c7f133248 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 03009084 |
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