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Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway.

机译:ip子苷是GLP-1受体的新型激动剂,可通过MAP激酶途径防止PC12细胞发生氧化损伤。

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摘要

Alzheimer's disease (AD) is the most common form of dementia. Glucagon-like peptide-1 (GLP-1) gives a new genre in therapeutic targets for intervention in AD with its neurotrophic and neuroprotective functions. In previous work, we identified that geniposide is a novel agonist for GLP-1 receptor, which shows neurotrophic characteristics to induce the neuronal differentiation of PC12 cells. The aim of this study is to determine whether geniposide prevents neurons from oxidative damage, and to explore its signaling pathways. The results demonstrated that geniposide increased the expression of anti-apoptotic proteins, including Bcl-2 and heme oxygenase-1 (HO-1), to antagonize the oxidative damage in PC12 cells induced by hydrogen peroxide. LY294002 (a PI3K inhibitor) inhibited the effect of geniposide increasing of Bcl-2 level by activation of MAPK, MEK and c-Raf phosphorylation in hydrogen peroxide treated PC12 cells. U0126 (a selective inhibitor of MEK) also attenuated the enhancement of geniposide on Bcl-2 level by inhibiting the phosphorylation of p90RSK in the hydrogen peroxide treated PC12 cells. All these data demonstrate that geniposide, an agonist for GLP-1 receptor, regulates expression of anti-oxidative proteins including HO-1 and Bcl-2 by activating the transcriptor of p90RSK via MAPK signaling pathway in PC12 cells.
机译:阿尔茨海默氏病(AD)是痴呆症的最常见形式。胰高血糖素样肽1(GLP-1)以其神经营养和神经保护功能为治疗AD的治疗靶标提供了新的类型。在以前的工作中,我们确定子苷是GLP-1受体的新型激动剂,它具有神经营养特性,可诱导PC12细胞的神经元分化。这项研究的目的是确定子苷是否可以防止神经元受到氧化损伤,并探索其信号传导途径。结果表明子苷可增加抗凋亡蛋白(包括Bcl-2和血红素加氧酶-1(HO-1))的表达,从而拮抗过氧化氢对PC12细胞的氧化损伤。 LY294002(PI3K抑制剂)通过过氧化氢处理的PC12细胞中MAPK,MEK和c-Raf磷酸化的活化,抑制了gen子苷Bcl-2水平的升高。 U0126(MEK的选择性抑制剂)还通过抑制过氧化氢处理的PC12细胞中p90RSK的磷酸化,减弱了gen子苷在Bcl-2水平上的增强作用。所有这些数据表明,子苷是GLP-1受体的激动剂,可通过PC12细胞中的MAPK信号通路激活p90RSK的转录子,从而调节包括HO-1和Bcl-2在内的抗氧化蛋白的表达。

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