EPO a Human
Description
Introduction to Erythropoietin (EPO) in Humans
Human erythropoietin (EPO) is a 30.4 kDa glycoprotein hormone critical for red blood cell (RBC) production. Composed of a 165-amino-acid backbone with four glycosylation sites (three N-linked and one O-linked glycan), its structure enables receptor binding and biological stability . Primarily synthesized in renal peritubular fibroblasts, EPO production is regulated by hypoxia-inducible transcription factors (HIFs), making it a key responder to tissue oxygen levels .
Alternative Splicing and Isoforms
The EPO gene produces splice variants, including EV-3 (hEPOΔ3), which lacks exon 3. EV-3 retains neuroprotective properties but lacks erythropoietic activity, detectable in human serum at 0.15–2.03 fmol/µg .
Synthesis and Regulation
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Primary sites: Kidneys (90% in adults), liver (fetal stage) .
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Hypoxia response: HIF-1α stabilization under low oxygen upregulates EPO transcription .
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Circulating levels: ~15 U/L (5 pmol/L) in healthy individuals, rising exponentially during anemia .
Erythropoiesis
EPO binds to erythroid progenitors in bone marrow, promoting survival, proliferation, and differentiation into RBCs .
Non-Hematopoietic Roles
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Neuroprotection: Reduces apoptosis in hippocampal neurons during oxygen-glucose deprivation .
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Cognitive enhancement: Improves verbal memory and recognition in depression trials .
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Organ protection: Antioxidant and anti-inflammatory effects in cardiac, renal, and retinal cells .
Labeled Indications
| Condition | CFDA Approval | FDA Approval |
|---|---|---|
| Anemia in chronic kidney disease | Yes | Yes (Epogen®) |
| Chemotherapy-induced anemia | Yes | Yes |
| Premature infant anemia | Yes | Off-label use |
Clinical Trials
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Treatment-resistant depression:
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Ischemic stroke:
Recombinant EPO (rhEPO) and Innovations
ELISA Quantification
| Parameter | Value |
|---|---|
| Sensitivity | 3.6–78.2 mIU/mL in serum/plasma |
| Intra-assay CV | 6.2% |
| Interfering factors | Hemolysis, lipemia |
Antibody Panels
The WHO EPO antibody panel (9 monoclonal antibodies) validates assay performance for neutralizing/non-neutralizing antibodies in clinical settings .
Future Directions
Product Specs
Erythropoietin-Alpha, EPO-a, EPO-alpha, EP, MGC138142.
Product Science Overview
Erythropoietin-Alpha (Human Recombinant), commonly known as epoetin alfa, is a biopharmaceutical product used to treat anemia, particularly in patients with chronic kidney disease, cancer, and other conditions that affect red blood cell production. This recombinant form of erythropoietin is produced using advanced genetic engineering techniques and has revolutionized the treatment of anemia.
The discovery of erythropoietin (EPO) dates back to the late 19th century when researchers observed a correlation between hypoxia (low oxygen levels) and increased red blood cell production. However, it wasn’t until 1977 that human erythropoietin was successfully purified from the urine of patients with aplastic anemia. In 1985, the human erythropoietin gene was cloned, paving the way for the production of recombinant erythropoietin .
Recombinant erythropoietin is produced using mammalian cell cultures, typically Chinese hamster ovary (CHO) cells. The production process involves transfecting these cells with the human erythropoietin gene, which is then integrated into the host cell’s genome. The cells are cultured in bioreactors, where they produce erythropoietin, which is subsequently purified for therapeutic use .
Erythropoietin is a glycoprotein, meaning it has carbohydrate side chains attached to its protein backbone. These glycan structures are crucial for the protein’s stability, activity, and half-life in the human body. The glycosylation process, which occurs in the endoplasmic reticulum and Golgi apparatus of the host cells, is complex and species-specific .
Erythropoietin is a cytokine that regulates erythropoiesis, the production of red blood cells. It acts on erythroid progenitor cells in the bone marrow, promoting their proliferation, differentiation, and maturation into red blood cells. The production of erythropoietin is primarily regulated by oxygen levels in the body. Under hypoxic conditions, the kidneys increase the production of erythropoietin to stimulate red blood cell production and improve oxygen delivery to tissues .
Recombinant erythropoietin has a wide range of clinical applications. It is primarily used to treat anemia associated with chronic kidney disease, where the kidneys’ ability to produce erythropoietin is impaired. It is also used in patients undergoing chemotherapy, those with HIV/AIDS, and in certain surgical settings to reduce the need for blood transfusions .
Erythropoietin-Alpha is one of the largest biopharmaceutical markets, with global sales reaching billions of dollars annually. The expiration of key process patents has led to the development of biosimilar products, increasing competition and accessibility in the market. Second-generation erythropoiesis-stimulating agents with improved pharmacokinetic properties have also been developed .
