Neurotrophic property of geniposide for inducing the neuronal differentiation of PC12 cells.
The emerging data show that the insulinotrophic hormone glucagon-like peptide-1(GLP-1) and its agonist extendin-4 have neurotrophic function to inducing neuronal differentiation of PC12 cells and prevent neurons damage challenged by oxidative stress. Here, with the model of high throughput screen for GLP-1 receptor agonists, we screen and identify that geniposide is a novel agonist for GLP-1 receptor. Furthermore, geniposide induces the neuronal differentiation of PC12 cells with resulting neurites outgrowth; we also observe an increase in expression of growth-associated protein-43. U0126, a selective MEK inhibitor, prevents neurites out growth and phosphorylation of mitogen-activated kinase proteins in PC12 cells induced by geniposide. All these results show that activation of GLP-1 receptor by geniposide to induce the neuronal differentiation of PC12 cells involves in MAPK signaling cascade.
Liu
Jianhui
J
Research Center of Pharmaceutical Chemistry & Chemobiology, Chongqing Technology and Business University, Chongqing 400067, China. jhliu@dlut.edu.cn
Zheng
Xuxu
X
Yin
Fei
F
Hu
Yinhe
Y
Guo
Lixia
L
Deng
Xiaohong
X
Chen
Gang
G
Jiajia
Jing
J
Zhang
Heng
H
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019922:GAP-43 Protein / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D039823:Iridoids / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects / Q000502:physiology; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D018027:Receptors, Glucagon / Q000502:physiology; D014162:Transfection / Q000379:methods
D002070:Butadienes; D004791:Enzyme Inhibitors; D019922:GAP-43 Protein; C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D039823:Iridoids; D018696:Neuroprotective Agents; D009570:Nitriles; D011714:Pyrans; D018027:Receptors, Glucagon; C113580:U 0126; C007835:geniposide; D005576:Colforsin; D052216:Glucagon-Like Peptide 1; D020932:Nerve Growth Factor; D008156:Luciferases; D020929:Mitogen-Activated Protein Kinase Kinases