Retinoid status and responsiveness to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking retinoid binding protein or retinoid receptor forms
| Autor: | Charlotte B. Nilsson, Abraham Brouwer, Christina Trossvik, Norbert B. Ghyselinck, Pi Hoegberg, Heinz Nau, A. Gerlienke Schuur, Helen Håkansson, Carsten K. Schmidt, Nicholas Fletcher, Pierre Chambon |
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| Přispěvatelé: | Chemistry and Biology, Institute for Environmental Studies, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Polychlorinated Dibenzodioxins
Time Factors Receptors Retinoic Acid MESH: Organ Size Retinoic acid Retinoid receptor Toxicology MESH: Dose-Response Relationship Drug Mice chemistry.chemical_compound 0302 clinical medicine MESH: Animals Retinoid 0303 health sciences Retinol Organ Size General Medicine Liver medicine.drug medicine.medical_specialty medicine.drug_class Tretinoin Biology Retinoid X receptor Retinoids 03 medical and health sciences Species Specificity Internal medicine medicine MESH: Species Specificity Animals MESH: Retinoids MESH: Mice 030304 developmental biology MESH: Receptors Retinoic Acid MESH: Tretinoin Dose-Response Relationship Drug MESH: Time Factors Body Weight Retinoid binding protein [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Retinol-Binding Proteins Cellular MESH: Retinol-Binding Proteins MESH: Body Weight MESH: Tetrachlorodibenzodioxin Retinol-Binding Proteins Retinol binding protein Endocrinology chemistry 030217 neurology & neurosurgery MESH: Liver |
| Zdroj: | Hoegberg, P, Schmidt, C K, Fletcher, N, Nilsson, C B, Trossvik, C, Gerlienke Schuur, A, Brouwer, A, Nau, H, Ghyselinck, N B, Chambon, P & Hakansson, H 2005, ' Retinoid status and responsiveness to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking retinoid binding protein or retinoid receptor forms ', Chemico-Biological Interactions, vol. 156, no. 1, pp. 25-39 . https://doi.org/10.1016/j.cbi.2005.06.006 Chemico-Biological Interactions, 156(1), 25-39. Elsevier Ireland Ltd Chemico-Biological Interactions Chemico-Biological Interactions, Elsevier, 2005, 156 (1), pp.25-39. ⟨10.1016/j.cbi.2005.06.006⟩ |
| ISSN: | 0009-2797 |
| DOI: | 10.1016/j.cbi.2005.06.006 |
| Popis: | International audience; We have investigated the role of Vitamin A (retinoid) proteins in hepatic retinoid processing under normal conditions and during chemical stress induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a chemical known to interfere with retinoid turnover and metabolism. Three separate studies were performed in wildtype control mice and transgenic mice that lack one or more isoforms of retinoic acid receptors (RAR), retinoid X receptors (RXR), or intracellular retinoid-binding proteins (CRABP I, CRABP II, CRBP I). Body and organ weight development was monitored from 2 weeks of age to adult, and hepatic levels of retinyl esters, retinol, and retinoic acid were investigated. In addition, hepatic concentrations of 9-cis-4-oxo-13,14-dihydro-retinoic acid, a recently discovered retinoid metabolite that has proven sensitive to both TCDD exposure and Vitamin A status, were also determined. Mice absent in the three proteins CRBP I, CRABP I, and CRABP II (CI/CAI/CAII-/-) displayed significantly lower hepatic retinyl ester, retinol, and all-trans-retinoic acid levels compared to wildtype mice, whereas the liver concentrations of 9-cis-4-oxo-13,14-dihydro-retinoic acid was considerably higher. After treatment with TCDD, hepatic total retinoids were almost entirely depleted in the CI/CAI/CAII-/- mice, whereas wildtype mice and mice lacking CRABP I, and CRABP II (CAI/CAII-/-) retained approximately 60-70% of their Vitamin A content compared to controls at 28 days. RAR and RXR knockout mice responded similarly to wildtype mice with respect to TCDD-induced retinoid disruption, with the exception of RXRbeta-/- mice which showed no decrease in hepatic Vitamin A concentration, suggesting that the role of RXRbeta in TCDD-induced retinoid disruption should be further investigated. Overall, the abnormal retinoid profile in the triple knockout mice (CI/CAI/CAII-/-), but not double knockout (CAI/CAII-/-) mice, suggests that a loss of CRBP I may account for the difference in retinoid profile in CI/CAI/CAII-/- mice, and is likely to result in an increased susceptibility to hepatic retinoid depletion following dioxin exposure. |
| Databáze: | OpenAIRE |
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