title: Erythropoietin attenuates advanced glycation endproducts-induced toxicity of Schwann cells in vitro.
abstract: 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.
authors.affiliation: Department of Anatomy, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, 250012, Shandong Province, China, foryuting@163.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Tianhua
authors.initials: T
authors.lastname: Chen
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Huaxiang
authors.initials: H
authors.lastname: Liu
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004921:Erythropoietin / Q000235:genetics / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000633:toxicity*; D066298:In Vitro Techniques; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics; D017467:Receptors, Erythropoietin / Q000235:genetics; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: C000593874:Ager protein, rat; D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D005978:Glutathione