Recombinant Human Erythropoietin/EPO (His, Flag)

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 the EPO protein is required for biological activities in vivo [4]. The mature human EPO protein shares 75% - 84% amino acid sequence identity with bovine, canine, equine, feline, mouse, ovine, porcine, and rat 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 erythropoietin 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 erythropoietin 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].

Reference

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[11]. Hardee, M.E. et al. (2006) Clin. Cancer Res. 12:332.

[12]. Verdier, F. et al. (2000) J. Biol. Chem. 275:18375.

[13]. Kertesz, N. et al. (2004) Dev. Biol. 276:101.