期刊
TOXICOLOGY IN VITRO
卷 39, 期 -, 页码 75-83出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2016.11.016
关键词
Sirtuins; Benzyl butyl phthalate (BBP); Mesenchymal stem cell; Adipogenesis; Hyperacetylation; Endocrine disruptor
类别
资金
- Texas AM University
- Texas A&M Health Science Center School of Pharmacy faculty development fund
Exposure to environmental chemicals can perturb an individual's metabolic set point, especially during critical periods of development, and as a result increase his or her propensity towards obesity that is manifested later in life and possibly in successive generations. We hypothesized that benzyl butyl phthalate (BBP), a widespread endocrine disruptor, may impair one important epigenetic regulator, sirtuin, in mesenchymal stem cells and induce adipogenesis. Our results showed that gene expression of two well-known adipogenic markers, aP2 and PPAR gamma, were significantly increased from day 2 to day 8 under 50 mu M BBP exposure when compared to control in C3H10T1/2 stem cells (p < 0.05) and induced adipogenesis. Sirt1 gene expression was also significantly decreased at day 2, 4, 6, and 8 (p < 0.05). However, Sirt7 gene expression was decreased only at day 2 and 8 (p < 0.05) while other sirtuin transcriptional levels remained unaltered throughout. Furthermore, Sirt1 and Sirt3 protein expression was decreased (p < 0.05) and overall protein hyperacetylation was observed at day 8. Furthermore, FOXO1 and beta-catenin, Sirt1 targets and adipogenesis regulators, were hyperacetylated at day 8. PGC1 alpha, NRF1, NRF2, and Tfam, were also significantly decreased (p < 0.05). In conclusion, our study suggests for the first time that BBP, a potential epigenetic disruptor, can lead to increased adipogenesis and metabolic dysregulation by impairing vital epigenetic regulators. (C) 2016 Elsevier Ltd. All rights reserved.
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