Hepatic biotransformation responses in Atlantic salmon exposed to retinoic acids and 3,3',4,4'-tetrachlorobiphenyl (PCB congener 77) |
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| Authors: | Arukwe Augustine Nordbø Bård |
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| Institution: | 1. Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity (CERAD), P.O. Box 5003, N-1432 Ås, Norway;2. Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo, Norway;3. Norwegian University of Life Sciences (NMBU), Department of Ecology and Natural Resource Management, P.O. Box 5003, N-1432 Ås, Norway;3. Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;4. Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou 571199, China;5. Department of Biochemistry, The University of Hong Kong, Hong Kong SAR, China;12. Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China;6. Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, China;1. Laboratory of Pneumology, Department of Experimental and Clinical Medicine, Katholieke Universiteit Leuven, Leuven, Belgium;2. Laboratory of Clinical and Experimental Endocrinology, Department of Experimental and Clinical Medicine, Katholieke Universiteit Leuven, Leuven, Belgium;1. Translational Oncogenomics Unit, Italian National Cancer Institute “Regina Elena”, 00144 Rome, Italy;2. Laboratory of Epigenetic, Molecular Medicine Area, Italian National Cancer Institute “Regina Elena”, 00144 Rome, Italy;3. HPC CINECA, 00185 Rome, Italy;4. Institute of Biomembranes and Bioenergetics of the National Research Council and Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, 70125 Bari, Italy;5. Molecular Chemoprevention Unit, Italian National Cancer Institute “Regina Elena”, 00144 Rome, Italy;6. Department of Oncology, McMaster University, Main Street West Hamilton, ON L8S 4K1, Canada;1. Nephrology Research, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA;2. Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA;3. Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA;4. Institute of Cardiovascular Sciences, University of Manchester, Manchester, M13 9PT, UK;5. University of Luxembourg, L-4365, Esch-sur-Alzette, Luxembourg |
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| Abstract: | Active derivatives of vitamin A are essential in physiological processes such as cell growth, differentiation, morphogenesis and development. The biological functions of vitamin A are mediated through the retinoid acid receptors (RARs) and retinoid X receptors (RXRs). Aryl hydrocarbon receptor (AhR) agonists such as planar halogenated compounds are known to interfere with vitamin A homeostasis in both field and laboratory studies. In this study, we have investigated the molecular interactions between vitamin A and AhR signalling pathways using juvenile Atlantic salmon and agonists for both receptor pathways. Groups of juvenile salmon were treated with all-trans- and 9-cis-retinoic acid mixture (7:3 ratio) dissolved in DMSO (dimethyl sulfoxide) at 0.1, 1 and 10 mg/kg fish weight. The mixture was force fed singly or in combination with 0.1 mg 3,3',4,4'-tetrachlorobiphenyl (co-planar congener 77)/kg fish weight dissolved in DMSO. Liver samples were collected 3 days after PCB-77 exposure. A separate group exposed to combined retinoic acid (1 mg/kg for 5 days) and PCB-77, was sampled at 3, 7 and 14 days after PCB-77 exposure. Liver samples collected from all exposure groups were analyzed for gene (RARalpha, AhR2alpha, AhR2beta, CYP1A1, UGT1 and GSTpi) expression using real-time PCR and activity (7-ethoxyresorufin O-deethylase (EROD), UGT and GST) using biochemical methods with specific substrates. Our data showed that exposure to RA alone did not produce a significant increase of RARalpha mRNA levels, and the presence of PCB-77 attenuated the expression of RARalpha in RA dose- and time-specific manner. In addition, RA produced a dose-dependent increase of CYP1A1 mRNA and activity (EROD) levels without concomitant increase in AhR2 isoforms. When administered alone, PCB-77 produced increased CYP1A1, UGT1 and GSTpi mRNA and enzyme levels. The PCB-77-induced CYP1A1, UGT1 and GSTpi (mRNA and activity) levels were modulated by RA, in a parameter and dose-specific manner. In general, our data show an interaction between vitamin A and AhR signalling that may affect retinoid homeostasis in fish. |
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