Insulin-like growth factor-1 protects SH-SY5Y cells against β-amyloid-induced apoptosis via the PI3K/Akt-Nrf2 pathway.

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.