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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
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
biological functions
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
therapeutic uses
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
rhu epo in treatment of anaemia of cancer
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
peptide mimetics
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
epo also has therapeutic ab uses
Epo also has therapeutic Abuses
  • Used in sports to improve endurance
  • now detected from naturally occurring EPO by protein markers appearing post-injection
erythropoietin receptor
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
optimum effect with 120 degree receptor angle
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’
stimulation of nuclear factor kappa b by epo
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
new evidence for epo in pns
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)
epo is protective in neural networks and during erthrocyte development

Epo is protective-in neural networksand during erthrocyte development

May be used in treatment of stroke victims

Protects against RBC apoptosis with NFkB stimulation

erythropoietin12

Erythropoietin:

Oxygen transport-protection-

Therapeutic uses-

and abuses !