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

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

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

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

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

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

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

Optimum Effect with 120 degree receptor angle n ‘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 n Not JAK2 dependent n NFkB described as control switch for gene transmission (on/off). n Protects against apoptosis n new evidence for neuroprotection

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

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

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