Apelin-13 Protects PC12 Cells from Corticosterone-Induced Apoptosis Through PI3K and ERKs Activation

It is widely accepted that environmental stress is a risk factor for mental disorders. Glucocorticoid hormones play a vital role in the regulation of physiological response to stress. High concentrations of corticosterone can induce cellular damage in PC12 cells, which possess typical neuronal features. Apelin and its receptor APJ are widely distributed in the central nervous system including limbic structures involved in stress responses. Previous studies have suggested that apelin has a neuroprotective function. However, the effect of apelin on corticosterone-induced neuronal damage remains to be elucidated. In the present study, we explored the potential protective activity of apelin-13 in PC12 cells treated with corticosterone and its underling mechanisms. The viability of the cells, the apoptosis of the cells, the level of phosphorylation of Akt (p-Akt) and extracellular signal-regulated kinases (p-ERKs) and cleaved caspase-3 expression were detected by MTT, Hoechst staining and flow cytometer assays and Western blotting. Results showed that corticosterone induced cells viability loss, cell apoptosis, down-regulation of p-Akt and p-ERKs and up-regulation of cleaved caspase-3. The effects induced by corticosterone were attenuated by apelin-13 pretreatment. Furthermore, apelin-13-mediated anti-viability loss, antiapoptosis and caspase-3 suppression activities were blocked by specific inhibitors of phosphatidylinositol 3-kinase (PI3K) (LY294002) and ERKs (PD98059). The data suggest that apelin-13 protects PC12 cells from corticosterone-induced apoptosis through activating PI3K/Akt and ERKs signaling pathways.