Ephrin-B2 inhibits Aβ25-35-induced apoptosis by alleviating endoplasmic reticulum stress and promoting autophagy in HT22 cells

Previous studies have shown that Erythropoietin-producing hepatocellular carcinoma receptor B2 (EphB2) inhibited Aβ-induced neuron Apoptosis and improved cognition in AD mice, but the role of which ligand Ephrin B2 (Ephrin-B2, efnB2) is not clear. The aim of this study was to investigate the effect of the efnB2-activated Eph/efn forward signaling pathway on Aβ-induced HT22 hippocampal cell Apoptosis using recombination mouse Ephrin B2-Fc chimera protein (efnB2-Fc). We found that non-toxic concentrations of efnB2-Fc decreased the release of Lactate Dehydrogenase (LDH) in HT22 cells and reduced cell Apoptosis in a dose-dependent manner. Further studies revealed that efnB2-Fc alleviated Aβ-induced ER stress and decreased the expression of ER-stress-related transcriptional factor C/EBP homologous protein (CHOP), binding immunoglobulin protein (Bip) and phosphorylated eukaryotic translation initiation factor 2 subunit α (p-eIF2α) in HT22 cells. These effects of efnB2-Fc were related to the inhibition of Akt/mTOR signal transduction, an increase in the level of microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ), and the activation of the Autophagy pathway. Our results indicate that the efnB2-mediated forward signaling pathway may activate the Autophagy pathway to alleviate the Aβ-induced ER stress and Apoptosis in the HT22 cell.