Fei Yin1, Jian-hui Liu, Xu-xu Zheng, Li-xia Guo. 1. Research Centre of Medicinal Chemistry and Chemical Biology, Chongqing Technology and Business University, Chongqing 400067, China.
Abstract
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.
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.
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