title: Insulin-like growth factor-1 protects SH-SY5Y cells against β-amyloid-induced apoptosis via the PI3K/Akt-Nrf2 pathway.
abstract: Insulin-like growth factor-1 (IGF-1) shows protective effect against Aβ-induced cytotoxicity and apoptosis, but the underlying mechanisms are poorly characterized. The present study was conducted to explore the mechanisms involved in the beneficial effect of IGF-1 against Aβ-induced apoptosis in SH-SY5Y cells. We found that pretreatment with IGF-1 attenuated Aβ25-35-induced loss of cell viability and apoptosis in SH-SY5Y cells in a dose-dependent manner. In addition, IGF-1 inhibited the generation of reactive oxygen species (ROS) and increased the antioxidant activity in Aβ25-35-treated cells. Further, IGF-1 significantly promoted the nuclear translocation of Nrf2, and upregulated the expression of its downstream gene heme oxygenase-1 (HO-1). Moreover, LY294002, a specific PI3K inhibitor, was found to completely abolish the protective effect of IGF-1 on Aβ25-35-induced apoptosis and ROS generation. Together, our findings suggest that IGF-1 protects SH-SY5Y cells against Aβ25-35-induced cell injury by scavenging ROS via the PI3K/Akt-Nrf2 signaling pathway.
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China; Department of Neurology, Jingshan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Zigao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Tinglin Hospital, Shanghai, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Neurology, Jingshan Hospital, Fudan University, Shanghai, PR China; Department of Neurology, Jining No.1 People's Hospital, Shandong, PR China.
authors.forename: Guanqun
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wan
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Chunjiu
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Department of Neurology, Jingshan Hospital, Fudan University, Shanghai, PR China. Electronic address: hbzyy8@sina.com.
authors.forename: Hengbing
authors.initials: H
authors.lastname: Zu
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D007334:Insulin-Like Growth Factor I; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Apoptosis; IGF-1; Nrf2; Oxidative stress; PI3K/Akt; β-amyloid