期刊
TOXICOLOGY LETTERS
卷 355, 期 -, 页码 141-149出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2021.12.001
关键词
Octocrylene; Peroxisome proliferator-activated receptor & nbsp;gamma ; Human bone marrow mesenchymal stem; cells; Obesogen; UV B filter
类别
资金
- MRC grant through the National Research Foundation of Korea (NRF) Korea [NRF-2018R1A5A2024425]
- National Research Foun-dation of Korea (NRF) [2019R1A2C2085749]
- National Research Foundation of Korea [2019R1A2C2085749] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Octocrylene (OC) is a widely used organic ultraviolet B filter, which has been detected in significant levels in marine and freshwater environments. This study found that OC promotes adiponectin production in human bone marrow mesenchymal stem cells, binds to PPARy, and alters the gene transcription profile of lipid-metabolism associated enzymes. These findings suggest that OC may act as a metabolic disrupting obesogen.
Octocrylene (OC) is an extensively prescribed organic ultraviolet B filter used in sunscreen products. Due to its extensive use, a significant level of OC is detected in marine and freshwater environments. Notably, the bioaccumulation of OC in aquatic biota may affect human health. In this study, the effect of OC on metabolism was investigated using the adipogenesis model of human bone marrow mesenchymal stem cells (hBM-MSCs). OC promoted adiponectin production during adipogenesis in hBM-MSCs compared to the vehicle-treated control (EC50, 29.6 mu M). In target identification, OC directly bound to peroxisome proliferator-activated receptor (PPAR) y (Ki, 37.8 mu M). OC-bound PPARy also significantly recruited nuclear receptor coactivator proteins SRC-1 (EC50, 54.1 mu M) and SRC-2 (EC50, 58.6 mu M). In the molecular docking simulation study, the optimal ligand-binding mode of OC suggested that OC is a PPARy partial agonist. A competitive analysis with a PPARy full agonist pioglitazone revealed that OC acted as a PPARy partial agonist. OC altered the gene transcription profile of lipid-metabolism associated enzymes in normal human keratinocytes, primarily exposed human cells after the application of sunscreens. In conclusion, OC is a potential metabolic disrupting obesogen. (C)& nbsp;2021 Published by Elsevier B.V.
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