Neuroprotection and CD131/GDNF/AKT Pathway of Carbamylated Erythropoietin in Hypoxic Neurons
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...
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| Published in | Molecular neurobiology Vol. 54; no. 7; pp. 5051 - 5060 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
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New York
Springer US
01.09.2017
Springer Nature B.V |
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| 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. |
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| AbstractList | 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. 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 [beta] receptor subunit ([beta]cR, 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. 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. |
| Author | Yu, Jie-Zhong Xiao, Bao-Guo Ma, Cun-Gen Wang, Xin Ding, Jing Lu, Chuan-Zhen Wang, Jing Li, Qin-Ying |
| Author_xml | – sequence: 1 givenname: Jing surname: Ding fullname: Ding, Jing organization: Department of Neurology, Zhongshan Hospital, Fudan University – sequence: 2 givenname: Jing surname: Wang fullname: Wang, Jing organization: Department of Neurology, Zhongshan Hospital, Fudan University – sequence: 3 givenname: Qin-Ying surname: Li fullname: Li, Qin-Ying organization: Institute of Neurology, Huashan Hospital, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University – sequence: 4 givenname: Jie-Zhong surname: Yu fullname: Yu, Jie-Zhong organization: Institute of Brain Science, Shanxi Datong University – sequence: 5 givenname: Cun-Gen surname: Ma fullname: Ma, Cun-Gen organization: Institute of Brain Science, Shanxi Datong University – sequence: 6 givenname: Xin surname: Wang fullname: Wang, Xin organization: Department of Neurology, Zhongshan Hospital, Fudan University – sequence: 7 givenname: Chuan-Zhen surname: Lu fullname: Lu, Chuan-Zhen organization: Institute of Neurology, Huashan Hospital, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University – sequence: 8 givenname: Bao-Guo surname: Xiao fullname: Xiao, Bao-Guo email: bgxiao@shmu.edu.cn organization: Institute of Neurology, Huashan Hospital, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27541284$$D View this record in MEDLINE/PubMed |
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| Snippet | Carbamylated erythropoietin (CEPO), an EPO derivative, is attracting widespread interest due to neuroprotective effects without erythropoiesis. However, little... |
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| SubjectTerms | AKT protein Animals Biomedical and Life Sciences Biomedicine Brain Cell Biology Cytokine Receptor Common beta Subunit - metabolism Enzyme-linked immunosorbent assay Erythropoiesis Erythropoietin Erythropoietin - analogs & derivatives Erythropoietin - pharmacology Female Glial cell line-derived neurotrophic factor Glial Cell Line-Derived Neurotrophic Factor - metabolism Glucose Glycoproteins Hypoxia Hypoxia - drug therapy Hypoxia - metabolism Immunocytochemistry Immunohistochemistry Mice Mice, Inbred C57BL Molecular modelling Neurobiology Neurogenesis Neurology Neuronal-glial interactions Neurons Neurons - drug effects Neurons - metabolism Neuroprotection Neuroprotection - drug effects Neuroprotective Agents - pharmacology Neurosciences Neutralization Oxygen Phosphorylation Polymerase chain reaction Proto-Oncogene Proteins c-akt - metabolism Rodents Signal Transduction - drug effects Variance analysis |
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| Title | Neuroprotection and CD131/GDNF/AKT Pathway of Carbamylated Erythropoietin in Hypoxic Neurons |
| URI | https://link.springer.com/article/10.1007/s12035-016-0022-0 https://www.ncbi.nlm.nih.gov/pubmed/27541284 https://www.proquest.com/docview/1923935035 https://search.proquest.com/docview/1859721580 |
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