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首页> 外文期刊>Life sciences >Extract of Ginkgo biloba induces phase 2 genes through Keap1-Nrf2-ARE signaling pathway.
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Extract of Ginkgo biloba induces phase 2 genes through Keap1-Nrf2-ARE signaling pathway.

机译：银杏叶提取物通过Keap1-Nrf2-ARE信号通路诱导2期基因。

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The standard extract of Ginkgo biloba (EGb) has been demonstrated to possess remarkable antioxidant activity in both cell lines and animals. However, the molecular mechanism underlying this effect is not fully understood. Phase 2 enzymes play important roles in the antioxidant system by reducing electrophiles and reactive oxygen species (ROS). We demonstrated that EGb induced typical phase 2 genes: glutamate cysteine ligase catalytic subunit (GCLC) and glutathione-S-transferase subunit-P1 (GST-P1), by real-time PCR. To investigate the molecular mechanism of this induction, we used quinone oxidoreductase 1 (NQO1) -- Antioxidant response element (ARE) reporter assay and found that EGb activated the activity of the wild type but not the one with ARE mutated. It indicated that EGb induced these genes through ARE, a cis-acting motif located in the promoter region of nearly all phase 2 genes. Since nuclear factor erythroid 2-related factor 2 (Nrf2) binds ARE to enhance the expression of phase 2 genes, we detected the Nrf2 content in nucleus and found an accumulation of Nrf2 stimulated by EGb. In a further test of Kelch-like ECH-associated protein 1 (Keap1), the repression protein of Nrf2 in the cytosol under resting condition, we found that Keap1 content was inhibited by EGb and then more Nrf2 would be released to translocate into nucleus. Thus, EGb was testified for the first time to induce the phase 2 genes through the Keap1-Nrf2-ARE signaling pathway, which is (or part of) the antioxidant mechanism of EGb.
机译：银杏的标准提取物（EGb）已被证明在细胞系和动物中均具有出色的抗氧化活性。但是，尚未完全了解这种作用的分子机制。 2相酶通过减少亲电试剂和活性氧（ROS）在抗氧化剂系统中发挥重要作用。我们通过实时PCR证明了EGb诱导典型的第2期基因：谷氨酸半胱氨酸连接酶催化亚基（GCLC）和谷胱甘肽-S-转移酶亚基-P1（GST-P1）。为了研究这种诱导的分子机制，我们使用了醌氧化还原酶1（NQO1）-抗氧化反应元件（ARE）报告基因检测，发现EGb激活了野生型的活性，但没有激活ARE突变的一种。这表明EGb通过ARE诱导了这些基因，ARE是位于几乎所有2期基因的启动子区域的顺式作用基序。由于核因子红系2相关因子2（Nrf2）结合ARE以增强2期基因的表达，因此我们检测了细胞核中Nrf2的含量并发现了由EGb刺激的Nrf2的积累。在进一步测试的Kelch样ECH相关蛋白1（Keap1）中，Nrf2的阻遏蛋白在静止状态下处于胞质溶胶中，我们发现Keap1的含量被EGb抑制，然后释放出更多的Nrf2从而转移到核中。因此，首次证明了EGb可以通过Keap1-Nrf2-ARE信号传导途径诱导2期基因，这是EGb的抗氧化机制（或其一部分）。

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