Apolipoprotein E protects astrocytes from hypoxia and glutamate-induced apoptosis

► ApoE protects astrocytes from hypoxia-induced apoptosis in a dose-dependent manner. ► The protective effect of apoE was mimicked by MK-801. ► ApoE decreased the hypoxia-induced level of extracellular glutamate of astrocytes. ► Elevated apoE secretion in astrocytes may be a novel strategy for neuronal protection. Apolipoprotein E (apoE) is predominantly synthesized by astrocytes in the brain. In this study, we investigated the role of apoE in astrocyte apoptosis. We demonstrated that apoE protects astrocytes from hypoxia-induced apoptosis in a dose-dependent manner. Glutamate release from astrocytic cultures is significantly lower from WT mice than from apoE knockout mice. Furthermore, the protective effect of apoE is mimicked by an NMDA receptor antagonist, MK-801. Finally, the apoE activator T0901317 significantly reduced the effect of glutamate-induced apoptosis of astrocytes. These results suggest that apoE protects astrocytes from hypoxia-induced apoptosis associated to NMDA receptor activation. Approaches that elevate apoE secretion in astrocytes might provide a novel strategy in the protection of neuronal ischemic injury.