GLP-1 receptor plays a critical role in geniposide-induced expression of heme oxygenase-1 in PC12 cells
GLP-1 receptor plays a critical role in geniposide-induced expression of heme oxygenase-1 in PC12 cells
复制标题
DOI：
10.1038/aps.2010.28
复制
发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
F. Yin;Jian-hui Liu;Xu Zheng;Li-Xia Guo
中科院分区：
文献类型：
--
作者：
F. Yin;Jian-hui Liu;Xu Zheng;Li-Xia Guo
目的：探讨京尼平苷对胰高血糖素样肽1受体（GLP-1 R）的激活及其相关细胞信号通路在细胞保护中的作用。Glp-1 r基因的敲除用shRNA进行。结果：京尼平苷可通过上调血红素加氧酶1（HO-1）的表达，抑制SIN-1诱导的PC 12细胞氧化损伤，其机制可能与上调cAMP-PKA-CREB信号通路有关。用HO-1基因的AB 1增强子阻断PC 12细胞后，京尼平苷诱导的荧光素酶活性呈剂量依赖性增加，但在Glp-1 r基因被阻断的PC 12细胞中没有这种作用。结论：GLP-1 R在京尼平苷诱导的HO-1表达中起重要作用，可减轻PC 12细胞的氧化损伤。
Aim:To explore the role of activation of glucagon-like peptide 1 receptor (GLP-1R) and its relative cell signaling pathway in the cytoprotection of geniposide.Methods:Cell viability was determined by MTT assay. Knockdown of the Glp-1r gene was carried out with shRNA. The levels of HO-1 protein and cAMP response element binding protein (CREB) phosphorylation were measured by Western blotting.Results:Geniposide protected PC12 cells from oxidative damage induced by 3-morpholinosydnonimine hydrochloride (SIN-1) by enhancing the expression of heme oxygenase 1 (HO-1) via the cAMP-PKA-CREB signal pathway. After transfecting PC12 cells with the AB1 enhancer from the HO-1 gene, luciferase activity induced by geniposide increased in a dose-dependent manner, but not in the PC12 cells whose Glp-1r gene was disrupted. Additionally, inhibition of HO-1 activity by Sn-protoporphyrin IX (SnPP) or shRNA-mediated knockdown of Glp-1r decreased the neuroprotection of geniposide in PC12 cells.Conclusion:GLP-1R plays a critical role in geniposide-induced HO-1 expression to attenuate oxidative insults in PC12 cells.