...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Ecotoxicology and Environmental Safety >In vitro assessment of effects of persistent organic pollutants on the transactivation of estrogen receptor α and β (ERα and ERβ) from the Baikal seal (Pusa sibirica)
【24h】

In vitro assessment of effects of persistent organic pollutants on the transactivation of estrogen receptor α and β (ERα and ERβ) from the Baikal seal (Pusa sibirica)

机译：持久性有机污染物对贝加尔湖海豹（Pusa sibirica）雌激素受体α和β（ERα和ERβ）反式激活的影响的体外评估

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

To assess the effect of exposure to persistent organic pollutants (POPs) on the estrogen receptor (ER) signaling pathway in Baikal seals (Pusa sibirica), we investigated the molecular characterizations and functions of two Baikal seal ER (bsER) isoforms, bsER alpha and bsER beta. The bsER alpha and bsER beta cDNA clones isolated have an open reading frame of 595 and 530 amino acid residues, respectively. The tissue distribution analyses of bsER mRNAs showed that bsER alpha transcripts were primarily found in the ovary and uterus, and bsER beta in the muscle in wild Baikal seals. The immunofluorescence staining assay showed that 17 beta-estradiol (E-2) treatment promoted the nuclear translocation of in vitro-expressed bsER alpha. Transient transfection of bsER alpha in U2OS cells enhanced the transcription of pS2, an ER target gene of E-2. We then measured bsER-mediated transactivation potencies of POPs in an in vitro reporter gene assay system, in which a bsER alpha or bsER beta expression vector was transfected into COS-1 cells. For comparison, transactivation potencies of POPs on mouse ERs (mER alpha and mER beta) were also evaluated in the same manner. Results showed significant dose-dependent responses of bsERs and mERs when treated with p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE). bsERs and mERs showed no response when exposed to polychlorinated biphenyls (PCBs) or 2,3,7,8-tetrachlorodibenzo-p-dioxin. Comparison of the dose-response curves of DDTs across species (bsERs vs. mERs) showed that bsER alpha had a response similar to mER alpha, but bsER beta was less sensitive than mER beta. Comparing the lowest observable effective concentrations of p,p'-DDT (2.8 mu M) and p,p'-DDE (10 mu M) for in vitro bsER alpha-mediated transactivation with their hepatic concentrations in wild Baikal seals indicated that some individuals accumulated these compounds at levels comparable to the effective concentrations, suggesting the potential disruption of the bsER alpha signaling pathway in the wild population by these compounds. Co-transfection experiments with bsER and the aryl hydrocarbon receptor (AHR) suggested that high accumulation of estrogenic compounds exerts a synergistic effect with dioxin-like congeners on ER signaling through AHR activation in the wild seal population.
机译：为了评估持久性有机污染物（POPs）暴露对贝加尔湖海豹（Pusa sibirica）雌激素受体（ER）信号传导途径的影响，我们调查了两种贝加尔湖海豹ER（bsER）亚型，bsERα和bsER的分子表征和功能bsER beta。分离的bsER alpha和bsER beta cDNA克隆的开放阅读框分别为595和530个氨基酸残基。 bsER mRNA的组织分布分析表明，bsER alpha转录本主要存在于卵巢和子宫中，而bsER beta则存在于野生贝加尔海豹体内的肌肉中。免疫荧光染色分析表明17β-雌二醇（E-2）处理促进了体外表达的bsERα的核易位。 bsER alpha在U2OS细胞中的瞬时转染增强了E-2的ER靶基因pS2的转录。然后，我们在体外报道基因测定系统中测量了bsER介导的POPs的反式激活能力，其中bsER alpha或bsER beta表达载体被转染到COS-1细胞中。为了进行比较，还以相同的方式评估了POP在小鼠ER（mER alpha和mER beta）上的反式激活能力。结果显示，当用p，p'-二氯二苯基三氯乙烷（p，p'-DDT）和p，p'-二氯二苯基二氯乙烯（p，p'-DDE）处理时，bsER和mER的剂量依赖性反应显着。当暴露于多氯联苯（PCB）或2,3,7,8-四氯二苯并-对-二恶英中时，bsER和mER没有反应。比较不同物种间滴滴涕的剂量反应曲线（bsER与mERs）表明，bsER alpha的反应与mER alpha类似，但bsER beta的敏感性低于mER beta。比较了在野生贝加尔湖海豹中，可观察到的最低的p，p'-DDT（2.8μM）和p，p'-DDE（10μM）体外bsERα介导的反式激活有效浓度与它们的肝浓度。这些化合物以与有效浓度相当的水平积累了这些化合物，表明这些化合物可能会破坏野生种群中的bsERα信号传导途径。使用bsER和芳基烃受体（AHR）进行的共转染实验表明，雌激素化合物的高积累通过野生型海豹种群中的AHR激活与二恶英样同源物对ER信号传导具有协同作用。

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