A new agonist of the erythropoietin receptor, Epobis, induces neurite outgrowth and promotes neuronal survival
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A new agonist of the erythropoietin receptor, Epobis, induces neurite outgrowth and promotes neuronal survival. / Pankratova, Stanislava; Gu, Bing; Kiryushko, Darya; Korshunova, Irina; Køhler, Lene B; Rathje, Mette; Bock, Elisabeth; Berezin, Vladimir.
In: Journal of Neurochemistry, Vol. 121, No. 6, 06.2012, p. 915-23.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - A new agonist of the erythropoietin receptor, Epobis, induces neurite outgrowth and promotes neuronal survival
AU - Pankratova, Stanislava
AU - Gu, Bing
AU - Kiryushko, Darya
AU - Korshunova, Irina
AU - Køhler, Lene B
AU - Rathje, Mette
AU - Bock, Elisabeth
AU - Berezin, Vladimir
N1 - © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.
PY - 2012/6
Y1 - 2012/6
N2 - Apart from its hematopoietic activity, erythropoietin (EPO) is also known as a tissue-protective cytokine. In the brain, EPO and its receptor are up-regulated in response to insult and exert pro-survival effects. EPO binds to its receptor (EPOR) via high- and low-affinity binding sites (Sites 1 and 2, respectively), inducing conformational changes in the receptor, followed by the activation of downstream signaling cascades. Based on the crystal structure of the EPO:EPOR(2) complex, we designed a peptide, termed Epobis, whose sequence encompassed amino acids from binding Site 1. The present study shows that the Epobis peptide specifically binds to EPOR and induces neurite outgrowth from primary neurons in an EPOR-expression dependent manner. Furthermore, Epobis promoted the survival of hippocampal and cerebellar neuronal cultures after kainate treatment and KCl deprivation, respectively. Thus, we identified a new functional agonist of EPOR with the potential to promote neuroregeneration and neuroprotection.
AB - Apart from its hematopoietic activity, erythropoietin (EPO) is also known as a tissue-protective cytokine. In the brain, EPO and its receptor are up-regulated in response to insult and exert pro-survival effects. EPO binds to its receptor (EPOR) via high- and low-affinity binding sites (Sites 1 and 2, respectively), inducing conformational changes in the receptor, followed by the activation of downstream signaling cascades. Based on the crystal structure of the EPO:EPOR(2) complex, we designed a peptide, termed Epobis, whose sequence encompassed amino acids from binding Site 1. The present study shows that the Epobis peptide specifically binds to EPOR and induces neurite outgrowth from primary neurons in an EPOR-expression dependent manner. Furthermore, Epobis promoted the survival of hippocampal and cerebellar neuronal cultures after kainate treatment and KCl deprivation, respectively. Thus, we identified a new functional agonist of EPOR with the potential to promote neuroregeneration and neuroprotection.
KW - Animals
KW - Blotting, Western
KW - Cell Survival
KW - Erythropoietin
KW - Gene Knockdown Techniques
KW - Humans
KW - Models, Molecular
KW - Neurites
KW - Neurons
KW - Neuroprotective Agents
KW - Peptides
KW - Protein Binding
KW - Protein Structure, Quaternary
KW - Rats
KW - Rats, Wistar
KW - Receptors, Erythropoietin
KW - Signal Transduction
KW - Surface Plasmon Resonance
KW - Transfection
U2 - 10.1111/j.1471-4159.2012.07751.x
DO - 10.1111/j.1471-4159.2012.07751.x
M3 - Journal article
C2 - 22469063
VL - 121
SP - 915
EP - 923
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 6
ER -
ID: 45118101