Moderate activation of autophagy regulates the intracellular calcium ion concentration and mitochondrial membrane potential in beta-amyloid-treated PC12 cells

•Beclin-1 dependent autophagy protect against Aβ1–42 induced cell injury.•Moderate activation of Beclin-1 dependent autophagy modulates Ca2+ homeostasis.•Moderate activation of Beclin-1 dependent autophagy maintains MMP.•Beclin-1 dependent autophagy may have a preventive function in AD. Alzheimer’s disease (AD) is an age-related and progressive neurodegenerative disease. Aggregated beta-amyloid (Aβ) disturbs Ca2+ homeostasis and causes mitochondrial dysfunction and finally underlies AD. Recent evidence suggests that autophagy initiation by Beclin-1 protein might be involved in the pathogenesis of AD. However, the effects of Beclin-1 dependent autophagy on intracellular calcium ion concentration ([Ca2+]i) and mitochondrial membrane potential (MMP) is unclear. The effects of Beclin-1 dependent autophagy that were activated by a gradient concentration of autophagy activator rapamycin or inhibited by autophagy inhibitor 3-methyladenine (3-MA) on cell viability and cell morphology were examined. Pretreatment with rapamycin significantly up-regulated the expression of Beclin-1 in response to Aβ1–42 application, but after pretreatment with 3-MA it was significantly down-regulated. Moderate activation of Beclin-1 dependent autophagy had an up regulation effect on cell viability and could maintain the original morphology of cells. Furthermore, rapamycin or 3-MA on [Ca2+]i and MMP in Aβ1–42 treatment of PC12 cells were evaluated. We also report that PC12 cells treated with Aβ1–42 showed an increase in [Ca2+]i but a decrease in MMP when compared to the normal control. However the application of rapamycin prior to this prevented the increase in [Ca2+]i and the decrease in MMP in response to Aβ1–42. When 3-MA was applied this exacerbated the effect of Aβ1–42 on the [Ca2+]i and the MMP. This shows that moderate activation of Beclin-1 dependent autophagy by rapamycin can modulate Ca2+ homeostasis and maintain MMP in response to Aβ1–42 induced cytotoxicity and so may have a preventive function in AD.