|Cell Proliferation Induced by Erythropoietin and Neutralization by Mouse Erythropoietin Antibody. Recombinant Mouse Erythropoietin (Catalog # 959‑ME) stimulates proliferation in the TF‑1 human erythroleukemic cell line in a dose-dependent manner (orange line). Proliferation elicited by Recombinant Mouse Erythropoietin (10 ng/mL) is neutralized (green line) by increasing concentrations of Rat Anti-Mouse Erythropoietin Monoclonal Antibody (Catalog # MAB9591). The ND50 is typically 0.15‑0.75 µg/mL.|
Erythropoietin (Epo) is a 34 kDa glycoprotein hormone in the type I cytokine family and is related to thrombopoietin (1). Its three N‑glycosylation sites, four alpha helices, and N- to C-terminal disulfide bond are conserved across species (2, 3). Glycosylation of Epo is required for biological activities in vivo (4). Mature mouse Epo shares 95% amino acid sequence identity with rat Epo and 73%‑82% with bovine, canine, equine, feline, human, ovine, and porcine EPO. Epo is primarily produced in the kidney by a population of fibroblast-like cortical interstitial cells adjacent to the proximal tubules (5). It is also produced in much lower, but functionally significant amounts by fetal hepatocytes and in adult liver and brain (6‑8). Epo promotes erythrocyte formation by preventing the apoptosis of early erythroid precursors which express the Epo receptor (Epo R) (8, 9). Epo R has also been described in brain, retina, heart, skeletal muscle, kidney, endothelial cells, and a variety of tumor cells (7, 8, 10, 11). Ligand induced dimerization of Epo R triggers JAK2-mediated signaling pathways followed by receptor/ligand endocytosis and degradation (1, 12). Rapid regulation of circulating Epo allows tight control of erythrocyte production and hemoglobin concentrations. Anemia or other causes of low tissue oxygen tension induce Epo production by stabilizing the hypoxia-induceable transcription factors HIF-1 alpha and HIF-2 alpha (1, 6). Epo additionally plays a tissue‑protective role in ischemia by blocking apoptosis and inducing angiogenesis (7, 8, 13).
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