title: Inhibiting receptor for advanced glycation end product (AGE) and oxidative stress involved in the protective effect mediated by glucagon-like peptide-1 receptor on AGE induced neuronal apoptosis.
abstract: Our previous study has demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonist could protect neurons from advanced glycation end products (AGEs) toxicity in vitro. However, further studies are still needed to clarify the molecular mechanism of this GLP-1 receptor -dependent action. The present study mainly focused on the effect of GLP-1 receptor agonists against the receptor for advanced glycation end products (RAGE) signal pathway and the mechanism underlying this effect of GLP-1. Firstly the data based on the SH-GLP-1R(+) and SH-SY5Y cells confirmed our previous finding that GLP-1 receptor could mediate the protective effect against AGEs. The assays of the protein activity and of the mRNA level revealed that apoptosis-related proteins such as caspase-3, caspase-9, Bax and Bcl-2 were involved. Additionally, we found that both GLP-1 and exendin-4 could reduce AGEs-induced reactive oxygen species (ROS) accumulation by suppressing the activity of nicotinamide adenine dinucleotide phosphate-oxidase. Interestingly, we also found that GLP-1 receptor activation could attenuate the abnormal expression of the RAGE in vitro and in vivo. Furthermore, based on the analysis of the protein expression and translocation level of transcription factor nuclear factor-κB (NF-κB), and the use of GLP-1 receptor antagonist exendin(9-39) and NF-κB inhibitor pyrrolidine dithiocarbamate, we found that the effect mediated by GLP-1 receptor could alleviate the over expression of RAGE induced by ligand via the suppression of NF-κB. In summary, the results indicated that inhibiting RAGE/oxidative stress was involved in the protective effect of GLP-1 on neuron cells against AGEs induced apoptosis.
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Feng-Mao
authors.initials: FM
authors.lastname: An
authors.affiliation: Medical School, Southeast University, Nanjing 210009, PR China.
authors.forename: Ai-Ran
authors.initials: AR
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: wbyao@cpu.edu.cn.
authors.forename: Wen-Bing
authors.initials: WB
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: xdgao@cpu.edu.cn.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D008297:Male; D008813:Mice, Inbred ICR; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D018384:Oxidative Stress; D010455:Peptides / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D015398:Signal Transduction; D014688:Venoms / Q000378:metabolism; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D010455:Peptides; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D014688:Venoms; D000077270:Exenatide; D019255:NADPH Oxidases; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: Alzheimer’s disease; Diabetes; Glucagon-like peptide-1 receptor; Oxidative stress; Receptor for advanced glycation end products