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首页> 外文期刊>Cell biology international. >EF24 prevents rotenone-induced estrogenic status alteration in breast cancer.
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EF24 prevents rotenone-induced estrogenic status alteration in breast cancer.

机译:EF24防止旋转酮诱导的雌激癌雌激素状态改变。

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摘要

Protein disulfide isomerase (PDI), an important endoplasmic reticulum-resident oxidoreductase chaperone can bind to estrogens as well as intact with its receptor proteins [i.e. estrogen receptors (ER) α and β]. It has been postulated that PDI also acts as an intracellular 17β-estradiol (E2)-binding protein that transports and accumulates E2 in live cells. Drop in E2 level promotes dissociation of E2 from PDI and released in cytosol; the released E2 can augment estrogen receptor-mediated transcriptional activity and mitogenic action in cultured cells by modulating the ERβ/ERα ratio. In this study, we observed rotenone-induced damage to PDI leads to significant increase in ERβ/ERα ratio by down-regulating ERα and up-regulating ERβ. We demonstrated that nitrosative stress induced disruption of the cellular estrogenic status can be prevented through diphenyl difluoroketone (EF24, curcumin analog) intervention by protecting PDI from reactive oxygen species (ROS)-induced damage. Together, our study suggests that both PDI and EF24 can play a vital role in maintaining cellular estrogenic homeostasis.
机译:蛋白质二硫化物异构酶(PDI),重要的内质网常规氧化还原酶伴侣可以与雌激素以及其受体蛋白完整结合[即雌激素受体(ER)α和β]。已经假设PDI也充当细胞内17β-雌二醇(E2) - 粘合蛋白,其在活细胞中运输和累积E2。 e2水平下降促进从PDI的e2解离并释放在细胞溶胶中;通过调节ERβ/ERα的比例,释放的E2可以增强雌激素受体介导的转录活性和促培养细胞中的促致动作用。在这项研究中,我们观察到Rotenone诱导的PDI损伤导致通过下调ERα和UP-COMMINATIONERβ的ERβ/ERα比的显着增加。我们证明,通过保护来自反应性氧(ROS)造成的损伤,可以通过二苯基二氟酮(EF24,姜黄素类似物)干预来防止亚硝化胁迫诱导的细胞雌激素状态的破坏。我们的研究表明,PDI和EF24都可以在维持细胞雌激素稳态方面发挥至关重要的作用。

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