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Erythropoietin

Erythropoietin. Known as EPO MW 30400Da Discovered by Miyake et al 1977from urine of anaemic pts. LC 4 alpha helical bundle class 1 cytokine 193 a.a. human (192 mouse) When levels low e.g.in CRF, chemotherapy treatment in cancer

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Erythropoietin

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  1. Erythropoietin • Known as EPO • MW 30400Da • Discovered by Miyake et al 1977from urine of anaemic pts. • LC 4 alpha helical bundle class 1 cytokine • 193 a.a. human (192 mouse) • When levels low e.g.in CRF, chemotherapy treatment in cancer • not effective when levels are high (high altitude, hypoxia due to CHD) • Has been used in AIDS

  2. Biological Functions • As its name suggests, EPO stimulates growth of Erythrocytes • It increases as a result of a negative feedback loop-low Oxygen=production of Epo. • Produced in the Kidneys and also in the Liver ( as Foetus: liver only) • Carries oxygen in blood

  3. Therapeutic Uses • When Epo levels low-used in aneamia resulting from chemotherapy, AIDS, CRF • Not useful if levels already high as in cases of hypoxia, high altitude living, CHD and lung disease. • Shown to improve QOL greatly in vast majority of cancer/AIDS pts

  4. RHu Epo in treatment of Anaemia of Cancer • Low levels of Epo resulting from the treatment of Cancer • treated by RHuEpo • improves Quality of life • improves anaemia in hypo-Epo cases

  5. Enables the use of Epo in therapy for CRF and cancer without unwanted immunological effects synthesised from random peptide ‘libraries’ displayed on filamentous phages ( Bacterial virus) These bind to and activate a receptor of cytokines similarly to original cytokine. 14-20 a.a. In length, serve as lead compounds for development of therapeutically effective Epo,smaller, less side effects Peptide Mimetics

  6. Epo also has therapeutic Abuses • Used in sports to improve endurance • now detected from naturally occurring EPO by protein markers appearing post-injection

  7. Erythropoietin Receptor • Hetero-dimer consisting of Beta sheets • Optimum effectiveness if 120 deg. to epo • works on JAK-stat pathway • stimulates NF-k B • protects against agoptosis

  8. Optimum Effect with 120 degree receptor angle • ‘Epo imposes a unique 120 degree angular orientation that is responsible for optimum signalling potential through intracellular kinase pathways’

  9. Stimulation of Nuclear Factor kappa B by Epo • Not JAK2 dependent • NFkB described as control switch for gene transmission (on/off). • Protects against apoptosis • new evidence for neuroprotection

  10. New Evidence for Epo in PNS • Thought to protect neural network by NF kappa B stimulation • Evidence that neuroprotective nature of Epo useful post-CVA • More evidence for neuroimmunomodulation (adds to Psychoneuroimmunological data)

  11. Epo is protective-in neural networksand during erthrocyte development May be used in treatment of stroke victims Protects against RBC apoptosis with NFkB stimulation

  12. Erythropoietin: Oxygen transport-protection- Therapeutic uses- and abuses !

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