GLP-1 receptor plays a critical role in geniposide-induced expression of heme oxygenase-1 in PC12 cells.
OBJECTIVE
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.


CONCLUSIONS
GLP-1R plays a critical role in geniposide-induced HO-1 expression to attenuate oxidative insults in PC12 cells.
Yin
Fei
F
Research Centre of Medicinal Chemistry and Chemical Biology, Chongqing Technology and Business University, Chongqing 400067, China.
Liu
Jian-hui
JH
Zheng
Xu-xu
XX
Guo
Li-xia
LX
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D000067757:Glucagon-Like Peptide-1 Receptor; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D039823:Iridoids / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D039823:Iridoids; D018696:Neuroprotective Agents; D018027:Receptors, Glucagon; C007835:geniposide; D051547:Heme Oxygenase-1; D017868:Cyclic AMP-Dependent Protein Kinases