title: Exendin-4, a glucagon-like peptide-1 receptor agonist, inhibits Aβ25-35-induced apoptosis in PC12 cells by suppressing the expression of endoplasmic reticulum stress-related proteins.
abstract: Neurodegenerative disorders are chronic and progressive disease. Exendin-4 (Ex-4) can function as a neuroprotective agent and has novel therapeutic ability for the treatment of neurodegenerative disorders. In this study, we aimed to explore the neuroprotective effect of Ex-4 on PC12 cell apoptosis induced by Aβ25-35 in molecular level. The apoptosis of PC12 cells was detected by MTT assay, TUNEL staining and flow cytometry. The expression of ERS (endoplasmic reticulum stress, ERS) related proteins such as CHOP, GRP78 and Caspase-12 were determined by Western blot and cell immunocytochemistry. Results showed the apoptotic rate of PC12 cells significantly increased after Aβ25-35 addition, which was remarkably reduced after Ex-4 treatment. The expression of CHOP, GRP78 and Caspase-12 were significantly upregulated, and then remarkably reduced after Ex-4 treatment, while in the presence of Exendin9-39, the effect of Ex-4 was reversed. In conclusion, endoplasmic reticulum stress might be involved in the apoptosis process of PC12 cell induced by Aβ25-35 and Ex-4 might provide a potential strategy for the treatment and prevention of cell apoptosis-associated disorders.
authors.affiliation: Department of Neurology, Jinshan Hospital Affiliated to Fudan University Shanghai 201508, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Jinshan Hospital Affiliated to Fudan University Shanghai 201508, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurology, Jinshan Hospital Affiliated to Fudan University Shanghai 201508, China.
authors.forename: Weichen
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Neurology, Jinshan Hospital Affiliated to Fudan University Shanghai 201508, China.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Jinshan Hospital Affiliated to Fudan University Shanghai 201508, China.
authors.forename: Hengbing
authors.initials: H
authors.lastname: Zu
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053454:Caspase 12 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000502:physiology; D000077270:Exenatide; D006360:Heat-Shock Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D051742:Transcription Factor CHOP / Q000378:metabolism; D014688:Venoms / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; C497251:Ddit3 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010455:Peptides; D014688:Venoms; C074636:amyloid beta-protein (25-35); D051742:Transcription Factor CHOP; D000077270:Exenatide; D053454:Caspase 12
keywords: Aβ25-35; Exendin-4; Neurodegenerative disorders; apoptosis; endoplasmic reticulum stress