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Characterization of the estrogenic effects of ginsenoside Rg1: Mechanism involved in achieving tissue selectivity.

机译:人参皂苷Rg1的雌激素作用的特征:实现组织选择性所涉及的机制。

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摘要

Our previous study demonstrated that ginsenoside Rg1 was a unique class of phytoestrogens which activated estrogen-like activities without direct interaction with the estrogen receptor (ER). The present study aims to investigate if Rg1 could exert tissue-selective estrogenic effects in ER-positive target tissues and the molecular mechanism involved in its tissue-selective estrogenic effects.;Our results demonstrated that the estrogenic actions of Rg1 were distinct from those of 17beta-estradiol and its effects were tissue selective. The potent estrogenic effect of Rg1 was only observed in mammary gland in immature female CD-1 mice. Chronic administration of Rg1 did not result in bone protective effects and unwanted simulation of reproductive tissues in OVX mice model in a way that was distinct from 17beta-estradiol which exerted bone protective effects and also the stimulatory effects in uterus. However, Rg1 exerted potential anti-apoptotic effects on cardiovascular tissues and estrogenic effects on brain tissues. In addition, we demonstrated that Rg1, but not estren, failed to exert stimulatory effects in UMR106 cells with expressed lower level of ER, suggesting that the estrogenic effects of Rg1 in bone may require higher abundance of ER. For the molecular mechanisms study, differential signaling pathways were involved in mediating the estrogenic actions of Rg1 in MCF-7 cells in comparison to 17beta-estradiol and estren. 17beta-estradiol decreased ERalpha protein expression in MCF-7 cells, but not Rg1 and estren. 17beta-estradiol increased ERalpha Ser 118 phosphorylation both in the cytoplasm and nucleus, especially in the nucleus. Rg1 increased ERalpha Ser 118 phosphorylation principally in the cytoplasm. Estren increased ERalpha Ser 118 phosphorylation pricipally in the nucleus. For the estrogen-related pS2 gene expression, both 17beta-estradiol and Rg1 increased pS2 mRNA expression in MCF-7 cells, while estren decreased pS2 mRNA expression. Additionally, both 17beta-estradiol and Rg1 induced the recruitment of co-activator SRC-1 to ERE-containing pS2 promoter, but not estren. Furthermore, we are the first to report the possible involvement of GPR30 pathway on the activation of MEK1/2 by Rg1 in MCF-7 cells.;In conclusion, the estrogenic effects of Rg1 might be tissue selective. The rapid ER-dependent signaling pathway was involved in the tissue-selective estrogenic effects of Rg1.
机译:我们以前的研究表明,人参皂苷Rg1是一类独特的植物雌激素,可激活类似雌激素的活性而不与雌激素受体(ER)直接相互作用。本研究旨在探讨Rg1是否能在ER阳性靶组织中发挥组织选择性雌激素作用及其涉及的组织选择性雌激素作用的分子机制。我们的结果证明Rg1的雌激素作用与17beta的不同-雌二醇及其作用具有组织选择性。仅在未成熟雌性CD-1小鼠的乳腺中观察到Rg1的有效雌激素作用。长期施用Rg1不会导致骨骼保护作用,并以不同于17β-雌二醇的方式在OVX小鼠模型中对生殖组织进行不必要的模拟,后者不同于在骨骼中具有骨骼保护作用和刺激作用的17β-雌二醇。但是,Rg1对心血管组织具有潜在的抗凋亡作用,对脑组织具有雌激素作用。此外,我们证明Rg1,而不是雌激素,在ER水平较低的UMR106细胞中未发挥刺激作用,提示Rg1在骨骼中的雌激素作用可能需要更高的ER含量。对于分子机制研究,与17β-雌二醇和雌激素相比,差异信号通路参与介导MCF-7细胞中Rg1的雌激素作用。 17β-雌二醇降低MCF-7细胞中ERalpha蛋白表达,但不降低Rg1和雌激素。 17β-雌二醇增加了ERalpha Ser 118在细胞质和细胞核中的磷酸化,尤其是在细胞核中。 Rg1主要在细胞质中增加ERalpha Ser 118磷酸化。 Estren主要在细胞核中增强ERalpha Ser 118磷酸化。对于雌激素相关的pS2基因表达,MC​​F-7细胞中17β-雌二醇和Rg1均增加pS2 mRNA表达,而雌激素则减少pS2 mRNA表达。此外,17β-雌二醇和Rg1都诱导共激活剂SRC-1募集到含有ERE的pS2启动子,但不是雌激素。此外,我们是第一个报道GPR30途径可能参与MCF-7细胞中Rg1激活MEK1 / 2的研究。总之,Rg1的雌激素作用可能是组织选择性的。快速ER依赖信号通路参与Rg1的组织选择性雌激素作用。

著录项

  • 作者

    Gao, Quangui.;

  • 作者单位

    Hong Kong Polytechnic University (Hong Kong).;

  • 授予单位 Hong Kong Polytechnic University (Hong Kong).;
  • 学科 Molecular biology.
  • 学位 Ph.D.
  • 年度 2012
  • 页码 288 p.
  • 总页数 288
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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