Tri-m-cresyl phosphate and PPAR/LXR interactions in seabream hepatocytes: revealed by computational modeling (docking) and transcriptional regulation of signaling pathways
| العنوان: | Tri-m-cresyl phosphate and PPAR/LXR interactions in seabream hepatocytes: revealed by computational modeling (docking) and transcriptional regulation of signaling pathways |
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| المؤلفون: | Augustine Arukwe, Paolo Cocci, Mauro Angeletti, Francesco Alessandro Palermo, Gilberto Mosconi, Graziano Aretusi, Matteo Mozzicafreddo |
| المصدر: | Toxicology Research. 5:471-481 |
| بيانات النشر: | Oxford University Press (OUP), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, chemistry.chemical_classification, Health, Toxicology and Mutagenesis, information science, Peroxisome proliferator-activated receptor, 010501 environmental sciences, Biology, Toxicology, 01 natural sciences, Fatty acid-binding protein, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, Biochemistry, chemistry, Transcriptional regulation, natural sciences, Binding site, Signal transduction, Liver X receptor, Transcription factor, Fatty acid synthesis, 0105 earth and related environmental sciences |
| الوصف: | The interactions between tri-m-cresyl phosphate (TMCP; an organophosphate flame retardant) and peroxisome proliferator activated receptors (PPARs) or liver X receptor α (LXRα) were investigated in seabream hepatocytes. The study was designed to characterize the binding of TMCP to PPARα, PPARγ and LXRα by computational modeling (docking) and transcriptional regulation of signaling pathways. TMCP mainly established a non-polar interaction with each receptor. These findings reflect the hydrophobic nature of this binding site, with fish LXRα showing the highest binding efficiency. Further, we have investigated the ability of TMCP to activate PPAR and LXR controlled transcriptional processes involved in lipid/cholesterol metabolism. TMCP induced the expression of all the target genes measured. All target genes were up-regulated at all exposure doses, except for fatty acid binding protein 7 (FABP7) and carnitine palmitoyltransferase 1B. Collectively, our data indicate that TMCP can affect fatty acid synthesis/uptake and cholesterol metabolism through LXRα and PPARs, together with interactions between these transcription factors in seabream liver. |
| تدمد: | 2045-4538 2045-452X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::744f36d5c51c0826d3ea22da01aca849Test https://doi.org/10.1039/c5tx00314hTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....744f36d5c51c0826d3ea22da01aca849 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20454538 2045452X |
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