Mechanism of Action
Erythropoietin has been shown to exert its effects by binding to the erythropoietin receptor (EpoR).
EPO is highly glycosylated (40% of total molecular weight), with half-life in blood around 5 hours. EPO's half-life may vary between endogenous and various recombinant versions. Additional glycosylation or other alterations of EPO via recombinant technology have led to the increase of EPO's stability in blood (thus requiring less frequent injections). EPO binds to the erythropoietin receptor on the red cell progenitor surface and activates a JAK2 signaling cascade. Erythropoietin receptor expression is found in a number of tissues such as the bone marrow and peripheral/central nervous tissue. In bloodstream, red cells themselves do not express erythropoietin receptor, and therefore cannot respond to EPO. However, indirect dependence of red cell longevity in the blood on plasma erythropoietin levels has been reported, a process termed neocytolysis.
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