Decabromodiphenyl ether-induced PRKACA hypermethylation contributed to glycolipid metabolism disorder via regulating PKA/AMPK pathway in rat and L-02 cells |
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| Institution: | 1. Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, 100069 Beijing, China;2. Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, 100069 Beijing, China;3. Haidian Maternal&Child Health Hospital, Health Care Department for Women, Beijing 100080, China;4. Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, China;1. SiPro Sicurezza e Produttività nel lavoro, Via Stimigliano 5, 00199 Rome, Italy;2. Department of Anatomy, Histology, Medical-Legal and the Orthopedics, Specialty School of Occupational Medicine, Unit of Occupational Medicine, University of Rome “ Sapienza ”, Rome, Italy;3. Department of Human Neurosciences, University of Rome “ Sapienza ”, Piazzale Aldo Moro 5, 00185 Rome, Italy;4. Croce Rossa Italiana (Italian Red Cross), Italy;1. School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, Jiangsu, China;2. Medical College of Soochow University, 199 Renai Road, Suzhou 215123, Jiangsu, China;1. Institute of Genetics, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China;2. School of nursing, Gansu University of Chinese Medicine, Lanzhou 730000, China;3. Laboratory Center for Medical Sciences, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China;4. Keylaboratory of Evidence Science Techniques Research and Application of Gansu Province, Gansu University of Political Science and Law, Lanzhou 730000, China;5. Institute of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China;1. Department of Clinical Analysis, Gerencia de Atención Integrada, Albacete, Spain;2. Pharmacology Consultant, Houston, TX, USA;3. Department of Anesthesiology, Gerencia de Atención Integrada, Albacete, Spain;1. Centro de Ciências do Mar (CCMAR), Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal;2. Instituto de Ciencias Marinas de Andalucía-ICMAN/CSIC, Campus Universitario Río San Pedro, Apdo. Oficial, 11510 Puerto Real, Cádiz, Spain;3. S2 AQUA – Sustainable and Smart Aquaculture Collaborative Laboratory, Olhão, Portugal;4. Aquaculture Research Center, Agro-Technological Institute of Castilla y León (ITACyL), Ctra. Arévalo, s/n, 40196 Zamarramala, Segovia, Spain;5. Centro Oceanográfico de Vigo, Instituto Español de Oceanografía (IEO-CSIC), 36390 Vigo, Spain;1. Gazi University, Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey;2. Department of Pharmaceutical Sciences, Aston University, Birmingham, United Kingdom |
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| Abstract: | BDE-209 is the most prevalent congener of polybrominated diphenyl ethers and has high bioaccumulation in humans and animals. BDE-209 has been reported to disrupt glycolipid metabolism, but the mechanisms are still unclear. In this study, we found that BDE-209 induced liver tissue injury and hepatotoxicity, increased the glucose and total cholesterol levels in the serum of rats, and increased glucose and triglyceride levels in L-02 cells. BDE-209 exposure changed the PKA, p-PKA, AMPK, p-AMPK, ACC, and FAS expression in rats’ liver and L-02 cells. Moreover, BDE-209 induced PRKACA-1 hypermethylation in L-02 cells. AMPK activator (AICAR) inhibited the changes of p-AMPK, ACC, and FAS expression and elevation of glucose and triglyceride levels induced by BDE-209. DNA methylation inhibitor (5-Aza-CdR) reversed BDE-209 induced alters of PKA/AMPK/ACC/FAS signaling pathway. These results demonstrated that BDE-209 could disrupt the glycolipid metabolism by causing PRKACA-1 hypermethylation to regulate the PKA/AMPK signaling pathway in hepatocytes. |
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| Keywords: | Decabromodiphenyl ether Glycolipid metabolism PKA/AMPK signaling pathway PRKACA DNA hypermethylation |
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