Erythropoietin protects neurons from apoptosis via activating PI3K/AKT and inhibiting Erk1/2 signaling pathway
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The aim of this study was to explore the neuroprotective effect and the underlying mechanism of erythropoietin (EPO) on the cortical neuronal cells insulted with oxygen and glucose deprivation (OGD). Different concentrations of EPO were used to determine the anti-apoptosis effect of EPO. In addition, PI3K inhibitor LY294002 and ERK1/2 inhibitor U0126 were added to explore the underlying mechanism of EPO. Cell apoptosis rate was measured by flow cytometry. The protein expression of Bax, Bcl-2, cleaved caspase-3, AKT, p-AKT, Erk1/2 and p-Erk1/2 wasmeasured by Western blot. Our results showed that EPO alleviates OGD-induced cell apoptosis in a dose-dependent manner; the neuroprotective effect of EPO was further confirmed by the fact that EPO treatment reversed the protein expression of cleaved caspase-3, as well as the Bcl-2/Bax ratio as compared with the OGD treatment. In the mechanism part, our results demonstrated that OGD and EPO nearly had no influence on the protein expression of AKT and Erk1/2 but altered the phosphorylation of them. Specifically, OGD decreased the expression of p-AKT and increased the expression of p-Erk1/2; while, EPO treatment reversed the expression of p-AKT and p-Erk1/2 as compared with OGD treatment. Interestingly, LY294002 decreased the expression of p-AKT and attenuated the neuroprotective effect of EPO; while, U0126 decreased the expression of p-Erk1/2 and enhanced the neuroprotective effect of EPO. Our study demonstrated that EPO protects neurons against apoptosis induced by OGD, which is closely related with activation of PI3K/AKT and inactivation of Erk1/2 signaling pathway.
KeywordsErythropoietin Neuroprotective agents PI3K/AKT Erk1/2
This study was sponsored by the Guizhou Science and Technology Cooperation Plan (Qian Ke He LH Zi 7022).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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