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Gene Review

Epo  -  erythropoietin

Rattus norvegicus

Synonyms: Erythropoietin
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Disease relevance of Epo


Psychiatry related information on Epo


High impact information on Epo

  • Erythropoietin, a kidney cytokine regulating haematopoiesis (the production of blood cells), is also produced in the brain after oxidative or nitrosative stress [9].
  • The regenerating liver produces erythropoietin in response to hypoxia [10].
  • Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis [11].
  • Although EPO is clearly antiapoptotic for neurons after experimental stroke, it is unknown whether EPO also directly modulates EPO receptor (EPO-R)-expressing glia, microglia, and other inflammatory cells [11].
  • We reasoned that benefits of EPO might be offset by increases in hematocrit and evaluated the direct effects of EPO in the ischemic heart [12].

Chemical compound and disease context of Epo


Biological context of Epo


Anatomical context of Epo

  • The authors examined the ability of EPO to modulate a series of death-related cellular pathways during free radical-induced injury in cerebral microvascular endothelial cells (ECs) [1].
  • Exogenous EPO maintains both genomic DNA integrity and cellular membrane asymmetry through parallel pathways that prevent the induction of Apaf-1 and preserve mitochondrial membrane potential in conjunction with enhanced Bcl-XL expression [1].
  • Erythropoietin (EPO) plays a prominent role in the regulation of the hematopoietic system, but the potential function of this trophic factor as a cytoprotectant in the cerebral vascular system is not known [1].
  • Furthermore, we show that EPO mediates the classic neurotrophic effects of proliferation, differentiation and maintenance in a dopaminergic cell line [2].
  • After HIF-1 activation the astrocytes express and release EPO [13].

Associations of Epo with chemical compounds

  • Thus, while vitamins E and C may have the potential to protect cells from oxidative damage, vitamin A exerts a specific stimulation of Epo production [14].
  • Vitamin A induced a dose-dependent increase (half-maximal stimulation at 0.2 microgram/ml) in the production of immunoreactive Epo during 24 hours of incubation (such as 680 +/- 51 U Epo/g cell protein in HepG2 cultures with 3 micrograms/ml retinol acetate compared to 261 +/- 15 U/g in untreated controls; N = 4) [14].
  • Because retinal ganglion cell (RGC) death is a common cause of reduced visual function in several ocular diseases, we explored whether Epo might potentially be beneficial in protecting RGCs from glutamate and nitric oxide (NO)-induced cytotoxicity, using isolated RGCs by a two-step panning method [15].
  • EPO suppressed Ca(2+)-induced dopamine release from PC12 cells in a concentration- and time-dependent manner [19].
  • However, in the presence of PD98,059, an inhibitor of ERK, and salicylic acid, an NF-kappaB inhibitor, the EPO-induced morphological differentiation of astrocytes and expression of FGAP and EPO receptor were reduced [20].

Physical interactions of Epo

  • These biological activities were completely inhibited by the anti-Epo antiserum and the extracellular domain of the Epo receptor capable of binding with Epo [16].

Regulatory relationships of Epo


Other interactions of Epo


Analytical, diagnostic and therapeutic context of Epo

  • Our results establish EPO as an important paracrine neuroprotective mediator of ischemic preconditioning [13].
  • Epo secretion significantly increased to 674 +/- 92 mU/g kidney (N = 7) when vitamins A (0.5 microgram/ml), E (0.5 microgram/ml) and C (10 micrograms/ml) in combination were added to the perfusion medium [14].
  • The effects of the single vitamins were studied in Epo-producing hepatoma cell cultures (lines HepG2 and Hep3B) [14].
  • CONCLUSIONS: These results demonstrate that liver-targeted pCAGGS-EpoR/IgG(1)Fc transfer by tail-vein injection with hydrodynamics-based transfection is useful for neutralizing Epo delivered by in vivo electroporation [27].
  • RT-PCR and Western blot analysis revealed that hypoxia-ischemia only marginally affected EPO expression [28].


  1. Apaf-1, Bcl-xL, cytochrome c, and caspase-9 form the critical elements for cerebral vascular protection by erythropoietin. Chong, Z.Z., Kang, J.Q., Maiese, K. J. Cereb. Blood Flow Metab. (2003) [Pubmed]
  2. Erythropoietin receptor is expressed on adult rat dopaminergic neurons and erythropoietin is neurotrophic in cultured dopaminergic neuroblasts. Csete, M., Rodriguez, L., Wilcox, M., Chadalavada, S. Neurosci. Lett. (2004) [Pubmed]
  3. Effects of erythropoietin on cardiac remodeling after myocardial infarction. Nishiya, D., Omura, T., Shimada, K., Matsumoto, R., Kusuyama, T., Enomoto, S., Iwao, H., Takeuchi, K., Yoshikawa, J., Yoshiyama, M. J. Pharmacol. Sci. (2006) [Pubmed]
  4. In vivo evidence that erythropoietin protects neurons from ischemic damage. Sakanaka, M., Wen, T.C., Matsuda, S., Masuda, S., Morishita, E., Nagao, M., Sasaki, R. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  5. Erythropoietin improves long-term spatial memory deficits and brain injury following neonatal hypoxia-ischemia in rats. Kumral, A., Uysal, N., Tugyan, K., Sonmez, A., Yilmaz, O., Gokmen, N., Kiray, M., Genc, S., Duman, N., Koroglu, T.F., Ozkan, H., Genc, K. Behav. Brain Res. (2004) [Pubmed]
  6. Mechanism of the decreased erythropoiesis in the water deprived rat. Giglio, J.M., Alippi, R.M., Barceló, A.C., Bozzini, C.E. Br. J. Haematol. (1979) [Pubmed]
  7. Maze learning impairment is associated with stress hemopoiesis induced by chronic treatment of aged rats with human recombinant erythropoietin. Rifkind, J.M., Abugo, O.O., Peddada, R.R., Patel, N., Speer, D., Balagopalakrishna, C., Danon, D., Ingram, D.K., Spangler, E.L. Life Sci. (1999) [Pubmed]
  8. Intracerebroventricular injection of erythropoietin enhances sleep in the rat. García-García, F., Krueger, J.M. Brain Res. Bull. (2003) [Pubmed]
  9. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Digicaylioglu, M., Lipton, S.A. Nature (2001) [Pubmed]
  10. Hepatic regeneration and erythropoietin production in the rat. Naughton, B.A., Kaplan, S.M., Roy, M., Burdowski, A.J., Gordon, A.S., Piliero, S.J. Science (1977) [Pubmed]
  11. Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. Villa, P., Bigini, P., Mennini, T., Agnello, D., Laragione, T., Cagnotto, A., Viviani, B., Marinovich, M., Cerami, A., Coleman, T.R., Brines, M., Ghezzi, P. J. Exp. Med. (2003) [Pubmed]
  12. A novel protective effect of erythropoietin in the infarcted heart. Parsa, C.J., Matsumoto, A., Kim, J., Riel, R.U., Pascal, L.S., Walton, G.B., Thompson, R.B., Petrofski, J.A., Annex, B.H., Stamler, J.S., Koch, W.J. J. Clin. Invest. (2003) [Pubmed]
  13. Erythropoietin is a paracrine mediator of ischemic tolerance in the brain: evidence from an in vitro model. Ruscher, K., Freyer, D., Karsch, M., Isaev, N., Megow, D., Sawitzki, B., Priller, J., Dirnagl, U., Meisel, A. J. Neurosci. (2002) [Pubmed]
  14. Effects of antioxidant vitamins on renal and hepatic erythropoietin production. Jelkmann, W., Pagel, H., Hellwig, T., Fandrey, J. Kidney Int. (1997) [Pubmed]
  15. Neuroprotective effects of erythropoietin on glutamate and nitric oxide toxicity in primary cultured retinal ganglion cells. Yamasaki, M., Mishima, H.K., Yamashita, H., Kashiwagi, K., Murata, K., Minamoto, A., Inaba, T. Brain Res. (2005) [Pubmed]
  16. A novel site of erythropoietin production. Oxygen-dependent production in cultured rat astrocytes. Masuda, S., Okano, M., Yamagishi, K., Nagao, M., Ueda, M., Sasaki, R. J. Biol. Chem. (1994) [Pubmed]
  17. Functional significance of erythropoietin receptor expression in breast cancer. Arcasoy, M.O., Amin, K., Karayal, A.F., Chou, S.C., Raleigh, J.A., Varia, M.A., Haroon, Z.A. Lab. Invest. (2002) [Pubmed]
  18. Erythropoietin and erythropoietin receptor expression after experimental spinal cord injury encourages therapy by exogenous erythropoietin. Grasso, G., Sfacteria, A., Passalacqua, M., Morabito, A., Buemi, M., Macrì, B., Brines, M.L., Tomasello, F. Neurosurgery (2005) [Pubmed]
  19. Erythropoietin inhibits calcium-induced neurotransmitter release from clonal neuronal cells. Kawakami, M., Iwasaki, S., Sato, K., Takahashi, M. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  20. EPO receptor-mediated ERK kinase and NF-kappaB activation in erythropoietin-promoted differentiation of astrocytes. Lee, S.M., Nguyen, T.H., Park, M.H., Kim, K.S., Cho, K.J., Moon, D.C., Kim, H.Y., Yoon, d.o. .Y., Hong, J.T. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  21. Erythropoietin protects the in vitro blood-brain barrier against VEGF-induced permeability. Martínez-Estrada, O.M., Rodríguez-Millán, E., González-De Vicente, E., Reina, M., Vilaró, S., Fabre, M. Eur. J. Neurosci. (2003) [Pubmed]
  22. Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats. Sola, A., Rogido, M., Lee, B.H., Genetta, T., Wen, T.C. Pediatr. Res. (2005) [Pubmed]
  23. Astroglial cytoprotection by erythropoietin pre-conditioning: implications for ischemic and degenerative CNS disorders. Diaz, Z., Assaraf, M.I., Miller, W.H., Schipper, H.M. J. Neurochem. (2005) [Pubmed]
  24. Erythropoietin gene transfer into rat testes by in vivo electropo-ration may reduce the risk of germ cell loss caused by cryptorchidism. Dobashi, M., Goda, K., Maruyama, H., Fujisawa, M. Asian J. Androl. (2005) [Pubmed]
  25. Hypoxic stress tolerance of the blind subterranean mole rat: expression of erythropoietin and hypoxia-inducible factor 1 alpha. Shams, I., Avivi, A., Nevo, E. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  26. Erythropoietin prevents early and late neuronal demise through modulation of Akt1 and induction of caspase 1, 3, and 8. Chong, Z.Z., Lin, S.H., Kang, J.Q., Maiese, K. J. Neurosci. Res. (2003) [Pubmed]
  27. Post-secretion neutralization of transgene-derived effect: soluble erythropoietin receptor/IgG1Fc expressed in liver neutralizes erythropoietin produced in muscle. Maruyama, H., Higuchi, M., Higuchi, N., Kameda, S., Saito, M., Sugawa, M., Matsuzaki, J., Neichi, T., Yokoyama, S., Miyazaki, Y., Miyazaki, J., Gejyo, F. The journal of gene medicine. (2004) [Pubmed]
  28. Hypoxia-ischemia affects erythropoietin and erythropoietin receptor expression pattern in the neonatal rat brain. Spandou, E., Papoutsopoulou, S., Soubasi, V., Karkavelas, G., Simeonidou, C., Kremenopoulos, G., Guiba-Tziampiri, O. Brain Res. (2004) [Pubmed]
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