title: Neuroprotection and CD131/GDNF/AKT Pathway of Carbamylated Erythropoietin in Hypoxic Neurons.
abstract: Carbamylated erythropoietin (CEPO), an EPO derivative, is attracting widespread interest due to neuroprotective effects without erythropoiesis. However, little is known about molecular mechanisms behind CEPO-mediated neuroprotection. In primary neurons with oxygen-glucose deprivation (OGD) and mice with hypoxia-reoxygenation, the neuroprotection and possible molecular mechanism of CEPO were performed by immunohistochemistry and immunocytochemistry, Western blot, RT-PCR, and ELISA. The comparisons were analyzed by ANOVA followed by unpaired two-tailed Student's t test. Both CEPO and EPO showed the neuroprotective effects in OGD model and hypoxic brain. CEPO did not trigger JAK-2 but activated AKT through glial cell line-derived neurotrophic factor (GDNF). It has been shown that CEPO acts upon a heteroreceptor complex comprising both the EPO receptor and the common β receptor subunit (βcR, also known as CD131). The blockage of CD131 reduced CEPO-mediated GDNF production, while GFR receptor blockage and GDNF neutralization inhibited CEPO-induced neurogenesis. Addition of GDNF to cultured neurons increased phosphorylation of AKT. CEPO protects neurons possible through the CD131/GDNF/AKT pathway.
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Neurology, Huashan Hospital, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
authors.forename: Qin-Ying
authors.initials: QY
authors.lastname: Li
authors.affiliation: Institute of Brain Science, Shanxi Datong University, Shanxi, 037009, China.
authors.forename: Jie-Zhong
authors.initials: JZ
authors.lastname: Yu
authors.affiliation: Institute of Brain Science, Shanxi Datong University, Shanxi, 037009, China.
authors.forename: Cun-Gen
authors.initials: CG
authors.lastname: Ma
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Neurology, Huashan Hospital, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
authors.forename: Chuan-Zhen
authors.initials: CZ
authors.lastname: Lu
authors.affiliation: Institute of Neurology, Huashan Hospital, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China. bgxiao@shmu.edu.cn.
authors.forename: Bao-Guo
authors.initials: BG
authors.lastname: Xiao
mesh_terms: D000818:Animals; D053648:Cytokine Receptor Common beta Subunit / Q000378:metabolism; D004921:Erythropoietin / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D000066829:Neuroprotection / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D053648:Cytokine Receptor Common beta Subunit; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; C488171:carbamylated erythropoietin; D004921:Erythropoietin; D051057:Proto-Oncogene Proteins c-akt
keywords: CD131; Carbamylated erythropoietin; Glial cell-derived neurotrophic factor; Neuroprotection