Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway
Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway
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京尼平苷是一种新型 GLP-1 受体激动剂，通过 MAP 激酶途径防止 PC12 细胞氧化损伤
DOI：
10.1016/j.neuint.2007.04.021
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发表时间：
2007-11-01
影响因子：
4.2
通讯作者：
Hu, Yinhe
中科院分区：
文献类型：
--
作者：
Liu, Jianhui;Yin, Fei;Hu, Yinhe
阿尔茨海默病 (AD) 是最常见的痴呆症。胰高血糖素样肽- I (GLP-1) 以其神经营养和神经保护功能为干预 AD 的治疗靶点提供了新的类型。在之前的工作中，我们发现京尼平苷是一种新型的 GLP-1 受体激动剂，具有神经营养特性，可诱导 PC 12 细胞的神经元分化。本研究的目的是确定 Gemposide 是否可以预防神经元免受氧化损伤，并探讨其信号通路。结果表明，gemposide 增加了抗凋亡蛋白的表达，包括 Bcl-2 和血红素加氧酶- I (HO-1)，以拮抗过氧化氢诱导的 PC] 2 细胞的氧化损伤。 LY294002（一种 PI3K 抑制剂）通过激活过氧化氢处理的 PC12 细胞中的 MAPK、MEK 和 c-Raf 磷酸化来抑制京尼平苷增加 Bcl-2 水平的作用。 U0126（MEK 的选择性抑制剂）还通过抑制过氧化氢处理的 PC 12 细胞中 p90RSK 的磷酸化，减弱京尼平苷对 Bcl-2 水平的增强作用。所有这些数据都表明，GLP-1受体激动剂京尼平苷通过MAPK信号通路激活p90RSK转录子，调节PC12细胞中HO-1和Bcl-2等抗氧化蛋白的表达。 (C) 2007 Elsevier Ltd. 保留所有权利。
Alzheimer's disease (AD) is the most common form of dementia. Glucagon-like peptide- I (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 PC 12 cells. The aim of this study is to determine whether gemposide prevents neurons from oxidative damage, and to explore its signaling pathways. The results demonstrated that gemposide increased the expression of anti-apoptotic proteins, including Bcl-2 and heme oxygenase- I (HO- 1), to antagonize the oxidative damage in PC] 2 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 PC 12 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. (C) 2007 Elsevier Ltd. All rights reserved.