交易激励
全氟辛酸
糖皮质激素受体
过氧化物酶体增殖物激活受体
受体
过氧化物酶体
化学
兴奋剂
核受体
人类健康
氨基酸
生物化学
生物
基因表达
转录因子
基因
医学
环境卫生
作者
Chang Wang,Huayu Fu,Jun Yang,Lei Liu,Fenghong Zhang,Chunyu Yang,Hongyuan Li,Jiamiao Chen,Qi Li,Xiaolin Wang,Yaorui Ye,Nan Sheng,Yong Guo,Jiayin Dai,Guowang Xu,Xinyu Liu,Jianshe Wang
标识
DOI:10.1016/j.jhazmat.2023.130831
摘要
Legacy per- and polyfluoroalkyl substances (PFASs) are a worldwide health concern due to their potential bioaccumulation and toxicity in humans. A variety of perfluoroether carboxylic acids (PFECAs) have been developed as next-generation replacements of legacy PFASs. However, information regarding their possible environmental and human health risks is limited. In the present study, we explored the effects of PFECAs on mice based on long-term exposure to environmentally relevant doses of perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoDA). Results showed that PFECAs exposure suppressed many cellular stress signals and resulted in hepatomegaly. PFO5DoDA acted as an agonist of the peroxisome proliferator-activated receptor (PPAR) in vitro and modulated PPAR-dependent gene expression in the liver. Importantly, PFECAs had an inhibitory effect on the glucocorticoid receptor (GR), which may contribute to the extensive suppression of stress signals. Of note, the GR suppression induced by PFECAs was not reported by legacy perfluorooctanoic acid (PFOA). PFO5DoDA-induced changes in both GR and PPAR signals remodeled hepatic metabolic profiles, including decreased fatty acids and amino acids and increased β-oxidation. Mechanistically, PFO5DoDA inhibited GR transactivation by degradation of GR proteins. Our results emphasize the potential risk of PFECAs to human health, which were introduced to ease concerns regarding legacy PFASs.
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