Advanced glycation endproducts (AGEs)-induced cytotoxicity is regarded as one of the main mechanisms responsible for neurological disorders. Although erythropoietin (EPO) is demonstrated to have neuroprotective effects in neurodegenerative diseases, the effects of EPO on AGEs-induced toxicity of Schwann cells (SCs) remain open for investigation. Primary cultured SCs isolated from 4 day-old Wistar rats were exposed to AGEs with or without EPO treatment for 5 days. AGEs decreased cell viability, increased apoptotic rate, elevated intracellular reactive oxygen species levels, and reduced total glutathione levels of SCs. The AGEs-induced toxic effects on SCs were partially blocked by AGER siRNA or AGER inhibitor FPS-ZM1. SCs exposed to AGEs exhibited higher mRNA and protein levels of receptor for AGEs (AGER), EPO, and EPO receptor (EPOR). Exogenous EPO treatment attenuated AGEs-induced oxidative stress and apoptosis probably by reducing the mRNA and protein expression of AGER. The protective effect of EPO against AGEs-induced toxicity was blocked by EPOR siRNA. The data of the present study gives, for the first time, evidence of the protective effects of EPO on SCs with AGEs-induced oxidative stress and apoptosis. These results imply that EPO might be a novel valuable agent for treating AGEs-induced toxicity.
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This work was supported by the National Natural Science Foundation of China (No. 81371929).
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The authors declare no conflicts of interest.
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Yu, T., Li, L., Chen, T. et al. Erythropoietin Attenuates Advanced Glycation Endproducts-Induced Toxicity of Schwann Cells In Vitro. Neurochem Res 40, 698–712 (2015). https://doi.org/10.1007/s11064-015-1516-2