Disease relevance of Epor

• Erythropoietin receptor-mediated inhibition of exocytotic glutamate release confers neuroprotection during chemical ischemia [1].
• Permanent focal cerebral ischemia activates erythropoietin receptor in the neonatal rat brain [2].
• Both, EPO and EPO receptor (EPOR) were found to be expressed after hypoxia in hippocampal neurons in vitro and in vivo [3].
• Erythropoietin receptor expression in adult rat cardiomyocytes is associated with an acute cardioprotective effect for recombinant erythropoietin during ischemia-reperfusion injury [4].
• An alternative splicing of the rat erythropoietin receptor (EpoR) gene was identified in normal and erythroleukemia cells [5].

High impact information on Epor

• We show that EPOR-mediated activation of Jak2 leads to phosphorylation of the inhibitor of NF-kappaB (IkappaB), subsequent nuclear translocation of the transcription factor NF-kappaB, and NF-kappaB-dependent transcription of neuroprotective genes [6].
• Unexpectedly, coadministration of MPSS antagonized the protective effects of EPO, even though the EPO receptor was up-regulated normally after injury [7].
• Modulation of wound healing because of administration of recombinant EPO or inhibition of endogenous EPO-EPO receptor correlated with changes in levels of inducible nitric oxide synthase protein in granulation tissue [8].
• We also found abundant expression of EPO receptor protein in macrophages, cells that play a pivotal role during wound healing [8].
• These results suggest that activation of EPO-R suppresses ischemic cell death by inhibiting the exocytosis of Glu [1].

Biological context of Epor

• Modulation of tumor apoptosis pathways by recombinant erythropoietin may have negative consequences by decreasing the chemosensitivity and radiosensitivity of erythropoietin receptor-positive breast tumors, although it did not have any obvious effects on growth with or without chemotherapy in this model [9].
• The ineffective erythropoiesis at 4 months after thymectomy was explained by the erythroblast LR/erythropoietin receptor (EPOR) dysfunction [10].

Anatomical context of Epor

• Erythropoietin receptor (EpoR) is expressed in the central nervous system (CNS), however, no clear consensus has been obtained whether Epo acts as a prosurvival factor in neurons [11].
• EPO receptor (EPOR) is also expressed in the cerebral cortex but its function is not known [12].
• In situ hybridization indicated that EPOR mRNA was upregulated in the periphery (ischemic penumbra) of a cerebrocortical infarct after occlusion of the middle cerebral artery, suggesting that an increased number of EPOR in neurons facilitates the EPO signal transmission, thereby preventing the damaged area from enlarging [12].
• EPO and EPO-R expression was determined by immunohistochemical analysis at 8 hours and at 2, 8, and 14 days in the spinal cord of injured and noninjured rats [13].
• Two weeks after injury, EPO immunoreactivity was scarcely detected in neurons, whereas glial cells and vascular endothelium expressed strong EPO-R immunoreactivity [13].

Associations of Epor with chemical compounds

• Inhibition was also produced by an EPO mimetic peptide 1 (EMP1), a small synthetic peptide agonist of EPO-R, but not by its inactive analogue in which Cys residues were substituted with Ser [14].
• STUDY DESIGN: This study localized the erythropoietin receptor in the cochlea and analyzed the effect of erythropoietin on gentamicin-damaged hair cells in vitro [15].

Physical interactions of Epor

• These biological activities were completely inhibited by the anti-Epo antiserum and the extracellular domain of the Epo receptor capable of binding with Epo [16].

Regulatory relationships of Epor

• Our results suggest a new mechanism for Epo-induced neuroprotection, in which circulating Epo controls and maintains the BBB through an Epo receptor signalling pathway and the re-establishment of cell junctions [17].
• Immunoanalyses showed that Epo induced a significant increase in phosphorylated Janus kinase 2 and signal transducer and activator of transcription-5 expressions at 1 and 3 d and up-regulated Bcl-xL expression by 24 h after FCI but did not affect Epo receptor or NF-kappaB expression [18].

Other interactions of Epor

• Hypoxia-ischemia affects erythropoietin and erythropoietin receptor expression pattern in the neonatal rat brain [19].

Analytical, diagnostic and therapeutic context of Epor

• Transcripts of EPO-R, VEGF-R1, and VEGF-R2 were detected by RT-PCR [20].
• Immunohistochemistry revealed that the erythropoietin receptor localizes to the outer and inner hair cells and supporting cells of the organ of Corti, as well as to the spiral ganglion cells and the stria vascularis [15].

References