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Erythropoietin - PowerPoint PPT Presentation

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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 CRF, chemotherapy treatment in cancer

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Erythropoietin l.jpg

  • 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 CRF, chemotherapy treatment in cancer

  • not effective when levels are high (high altitude, hypoxia due to CHD)

  • Has been used in AIDS

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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

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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

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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

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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

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Epo also has therapeutic unwanted immunological effectsAbuses

  • Used in sports to improve endurance

  • now detected from naturally occurring EPO by protein markers appearing post-injection

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Erythropoietin Receptor unwanted immunological effects

  • 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

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Optimum Effect with 120 degree receptor angle unwanted immunological effects

  • ‘Epo imposes a unique 120 degree angular orientation that is responsible for optimum signalling potential through intracellular kinase pathways’

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Stimulation of Nuclear Factor kappa B by Epo unwanted immunological effects

  • Not JAK2 dependent

  • NFkB described as control switch for gene transmission (on/off).

  • Protects against apoptosis

  • new evidence for neuroprotection

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New Evidence unwanted immunological effects 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 l.jpg

Epo is unwanted immunological effectsprotective-in neural networksand during erthrocyte development

May be used in treatment of stroke victims

Protects against RBC apoptosis with NFkB stimulation

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Erythropoietin: unwanted immunological effects

Oxygen transport-protection-

Therapeutic uses-

and abuses !