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1,3-dichloro-2-propanol induced lipid accumulation in HepG2 cells through cAMP/protein kinase A and AMP-activated protein kinase pathways via Gi/o-coupled receptors
Affiliation:1. Department of food quality and safety, Jilin University, Changchun, Jilin 130062, People’s Republic of China;2. College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, People’s Republic of China;1. Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan;2. Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan;3. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan;4. Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan;5. Department of Styling & Cosmetology, Hsin Sheng Junior College of Medical Care and Management, Taoyuan, Taiwan;6. Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan;7. School of Medicine, Chung Shan Medical University, Taichung, Taiwan;8. Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan;9. VYM Genome Research Center, National Yang-Ming University, Taipei, Taiwan;1. Clermont Université, Université d’Auvergne, EA7280, Laboratoire de Neuropsychopharmacologie des systèmes dopaminergiques sous corticaux, Clermont-Ferrand, France;2. CHU Clermont-Ferrand, Service de Neurologie, 63000 Clermont-Ferrand, France;1. Diabetes and Nutritional Sciences Division, School of Medicine, King''s College London, Franklin-Wilkins Building, London SE1 9NH, United Kingdom;2. Faculty of Medicine, Nutrition and Dietetics Research Group, Division of Diabetes, Endocrinology and Metabolism, Department of Investigative Medicine, Imperial College London, London W12 0NN, United Kingdom;3. Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, United Kingdom;4. Health Sciences Research Centre, Whitelands College, University of Roehampton, London SW15 5PU, United Kingdom;5. Nutritional Sciences, University of Surrey, Leggett Building, Guildford, Surrey GU2 7WG, United Kingdom
Abstract:1,3-dichloro-2-propanol (1,3-DCP) is a food born hepatoxic chloropropanol contaminant that has been detected in a wide range of foods. In the present study, we investigated the effects and mechanisms of 1,3-DCP on lipid accumulation in HepG2 cells. The data showed 1,3-DCP significantly increased intracellular content of triglyceride (TG) and total cholesterol (TC) at 0.5–2 μg/mL. Further results showed that 1,3-DCP greatly decreased cyclic AMP (cAMP) level. In addition, 1,3-DCP inhibited PKA and AMPK signaling pathway, but had no influence on intracellular calcium and regulated proteins. Moreover, Gi/o protein inhibitor PTX significantly inhibited 1,3-DCP induced decrease of cAMP, p-PKA and p-AMPK expression. Furthermore, 1,3-DCP significantly decreased GPR41 and GPR43 expression, but had no effect on GPR109B.Thus, we concluded that 1,3-DCP induced lipid accumulation in HepG2 cells through cAMP/PKA and AMPK signaling pathways via Gi/o-coupled receptor.
Keywords:1,3-DCP  Lipid accumulation  cAMP  PKA  AMPK  Gi/o
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