促红细胞生成素 EPO

刺激骨髓红细胞生成 / 糖蛋白造血因子：结合骨髓红系祖细胞 EPOR 受体，激活 JAK2/STAT5 抑制凋亡并促进红细胞增殖分化，提高血红蛋白与血氧运载能力

大幅增加血液中红细胞数量，极大地提升血氧运载能力和肌肉供氧。用于治疗严重贫血，也是耐力型运动中突破携氧极限的核心物质。

Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bone marrow. Low levels of EPO (around 10 mU/mL) are constantly secreted in sufficient quantities to compensate for normal red blood cell turnover. Common causes of cellular hypoxia resulting in elevated levels of EPO (up to 10 000 mU/mL) include any anemia, and hypoxemia due to chronic lung disease.

Erythropoietin is largely synthesized in the deep renal cortex by peritubular interstitial fibroblast-like cells, namely located primarily in close association with the peritubular capillaries and proximal convoluted tubule; it is also produced in perisinusoidal cells in the liver. Liver production predominates in the fetal and perinatal period; renal production predominates in adulthood. It is homologous with thrombopoietin.

Exogenous erythropoietin, recombinant human erythropoietin (rhEPO), is produced by recombinant DNA technology in cell culture and are collectively called erythropoiesis-stimulating agents (ESA): two examples are epoetin alfa and epoetin beta. ESAs are used in the treatment of anemia in chronic kidney disease, anemia in myelodysplasia, and in anemia from cancer chemotherapy. Risks of therapy include death, myocardial infarction, stroke, venous thromboembolism, and tumor recurrence. Risk increases when EPO treatment raises hemoglobin levels over 11 g/dL to 12 g/dL: this is to be avoided.

rhEPO has been used illicitly as a performance-enhancing drug. It can often be detected in blood, due to slight differences from the endogenous protein; for example, in features of posttranslational modification.

Source: English Wikipedia, "Erythropoietin".

Erythropoietin has been shown to exert its effects by binding to the erythropoietin receptor (EpoR). EPO binds to the erythropoietin receptor on the red cell progenitor surface and activates a JAK2 signalling cascade. This initiates the STAT5, PIK3 and Ras MAPK pathways. This results in differentiation, survival and proliferation of the erythroid cell. SOCS1, SOCS3 and CIS are also expressed which act as negative regulators of the cytokine signal.

High level erythropoietin receptor expression is localized to erythroid progenitor cells. While there are reports that EPO receptors are found in a number of other tissues, such as heart, muscle, kidney and peripheral/central nervous tissue, those results are confounded by nonspecificity of reagents such as anti-EpoR antibodies. In controlled experiments, a functional EPO receptor is not detected in those tissues. In the bloodstream, red cells themselves do not express erythropoietin receptor, so 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. In addition, there is conclusive evidence that EPO receptor expression is upregulated in brain injury.

^ Middleton SA, Barbone FP, Johnson DL, Thurmond RL, You Y, McMahon FJ, et al. (May 1999). "Shared and unique determinants of the erythropoietin (EPO) receptor are important for binding EPO and EPO mimetic peptide". The Journal of Biological Chemistry. 274 (20): 14163–14169. doi:10.1074/jbc.274.20.14163. PMID 10318834.

^ Livnah O, Johnson DL, Stura EA, Farrell FX, Barbone FP, You Y, et al. (November 1998). "An antagonist peptide-EPO receptor complex suggests that receptor dimerization is not sufficient for activation". Nature Structural Biology. 5 (11): 993–1004. doi:10.1038/2965. PMID 9808045. S2CID 24052881.

^ Kasper C (2003). "Erythropoietin". The Cytokine Handbook. pp. 149–166. doi:10.1016/B978-012689663-3/50011-9. ISBN 978-0-12-689663-3.