...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Chemosphere >Endocrine activities and adipogenic effects of bisphenol AF and its main metabolite
【24h】

Endocrine activities and adipogenic effects of bisphenol AF and its main metabolite

机译：双酚AF及其主要代谢产物的内分泌活性和成脂作用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Bisphenol AF (BPAF) is a fluorinated analog of bisphenol A (BPA), and it is a more potent estrogen receptor (ER) agonist. BPAF is mainly metabolized to BPAF-glucuronide (BPAF-G), which has been reported to lack ER agonist activity and is believed to be biologically inactive. The main goal of the current study was to examine the influence of the metabolism of BPAF via glucuronidation on its ER activity and adipogenesis. Also, as metabolites can have different biological activities, the effects of BPAF-G on other nuclear receptors were evaluated. First, in-vitro BPAF glucuronidation was investigated using recombinant human enzymes. Specific reporter-gene assays were used to determine BPAF and BPAF-G effects on estrogen, androgen, glucocorticoid, and thyroid receptor pathways, and on PXR, FXR, and PPAR gamma pathways. Their effects on lipid accumulation and differentiation were determined in murine 3T3L1 preadipocytes using Nile Red, with mRNA expression analysis of the adipogenic markers adiponectin, Fabp4, Cebp alpha, and PPAR gamma. BPAF showed strong agonistic activity for hER alpha and moderate antagonistic activities for androgen and thyroid receptors, and for PXR. BPAF-G was antagonistic for PXR and PPAR gamma. BPAF (0.1 mu M) and BPAF-G (1.0 mu M) induced lipid accumulation and increased expression of key adipogenic markers in murine preadipocytes. BPAF-G is therefore not an inactive metabolite of BPAF. Further toxicological and epidemiological investigations of BPAF effects on human health are warranted, to provide better understanding of the metabolic end-elimination of BPAF. (C) 2018 Elsevier Ltd. All rights reserved.
机译：双酚AF（BPAF）是双酚A（BPA）的氟化类似物，并且是更有效的雌激素受体（ER）激动剂。 BPAF主要代谢为BPAF-葡糖醛酸（BPAF-G），据报道该蛋白缺乏ER激动剂活性，被认为具有生物活性。本研究的主要目的是研究通过葡萄糖醛酸化作用对BPAF的代谢对其ER活性和脂肪形成的影响。另外，由于代谢物可能具有不同的生物学活性，因此评估了BPAF-G对其他核受体的作用。首先，使用重组人酶研究了体外BPAF葡萄糖醛酸苷化。使用特定的报告基因测定法来确定BPAF和BPAF-G对雌激素，雄激素，糖皮质激素和甲状腺受体途径以及PXR，FXR和PPARγ途径的影响。使用尼罗红在鼠3T3L1前脂肪细胞中确定了它们对脂质蓄积和分化的影响，并对脂肪形成标记脂联素，Fabp4，Cebp alpha和PPARγ的mRNA表达进行了分析。 BPAF对hERα具有强烈的激动作用，对雄激素和甲状腺受体以及PXR具有中等拮抗作用。 BPAF-G对PXR和PPARγ具有拮抗作用。 BPAF（0.1μM）和BPAF-G（1.0μM）诱导脂质积累，并在鼠前脂肪细胞中增加主要脂肪形成标记的表达。因此，BPAF-G不是BPAF的非活性代谢产物。有必要对BPAF对人类健康的影响进行进一步的毒理学和流行病学研究，以更好地了解BPAF的代谢最终消除作用。 （C）2018 Elsevier Ltd.保留所有权利。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号