Recombinant Human Erythropoietin/EPO

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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[10]. Acs, G. et al. (2001) Cancer Res. 61:3561.

[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.