Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway.
Alzheimer's disease (AD) is the most common form of dementia. Glucagon-like peptide-1 (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 PC12 cells. The aim of this study is to determine whether geniposide prevents neurons from oxidative damage, and to explore its signaling pathways. The results demonstrated that geniposide increased the expression of anti-apoptotic proteins, including Bcl-2 and heme oxygenase-1 (HO-1), to antagonize the oxidative damage in PC12 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 PC12 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.
Liu
Jianhui
J
Research Center of Pharmaceutical Chemistry & Chemobiology, Chongqing Technology and Business University, Chongqing 400067, China. jhliu@ctbu.edu.cn
Yin
Fei
F
Zheng
Xuxu
X
Jing
Jiajia
J
Hu
Yinhe
Y
D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D039823:Iridoids / Q000494:pharmacology* / Q000627:therapeutic use; D020930:MAP Kinase Kinase Kinases / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000187:drug effects / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D018027:Receptors, Glucagon / Q000819:agonists* / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000187:drug effects / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D039823:Iridoids; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011714:Pyrans; D018027:Receptors, Glucagon; C007835:geniposide; D052216:Glucagon-Like Peptide 1; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; D019908:Proto-Oncogene Proteins c-raf; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D020930:MAP Kinase Kinase Kinases