BCL-2-associated athanogene-1 (BAG-1) is a multifunctional protein that was first identified as a binding partner of BCL-2. Our previous results indicated that BAG-1 large (BAG-1L) overexpression significantly increases cell viability and decreases apoptosis by upregulating HSP70 and p-AKT in response to hypoxia/reoxygenation in SY-SH5Y cells. However, the functional domain of BAG-1L that exerts these protective effects against hypoxic damage has not been identified. In this study, we examined changes in HSP70 and p-AKT protein levels in SH-SY5Y cells with or without BAG-1L domain mutation after six hours of hypoxia/reoxygenation treatment. The BAG-1 domain mutant (BAG-1MUT) attenuated neuronal viability and proliferation while enhancing apoptosis after hypoxia/reoxygenation, which was achieved in part by inhibiting the HSP70 and p-AKT signalling pathways. This evidence illustrates that the BAG-1 domain plays a key role in protecting cells from hypoxia/reoxygenation injury.
Keywords: Apoptosis; BAG-1; HSP70; Ischaemia; PI3K/AKT.
Copyright © 2020 Elsevier B.V. All rights reserved.