Epo and non-hematopoietic cells: What do we know?

Methods in Molecular Biology

Volumn 982, Issue , 2013, Pages 13-41

  Ogunshola, Omolara O ^a   Bogdanova, Anna Yu ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

Adult kidney; Fetal liver; HIF; Non hematopoietic cells

Indexed keywords

ERYTHROPOIETIN; ERYTHROPOIETIN RECEPTOR; NEUROTRANSMITTER;

ANGIOGENESIS; ARTICLE; AUTOCRINE EFFECT; BRAIN DEVELOPMENT; CALCIUM TRANSPORT; CELL DIFFERENTIATION; CELL PROLIFERATION; ENDOTHELIUM CELL; ERYTHROID PRECURSOR CELL; ERYTHROPOIESIS; FETUS LIVER; HEART DEVELOPMENT; HORMONE ACTION; HUMAN; HYPOXIA; INJURY; KIDNEY; NONHUMAN; PARACRINE SIGNALING; PHENOTYPE; PRIORITY JOURNAL; ANIMAL; BIOLOGICAL MODEL; LIVER; METABOLISM; REVIEW;

ANIMALS; ERYTHROPOIETIN; HUMANS; KIDNEY; LIVER; MODELS, BIOLOGICAL;

EID: 84882741604     PISSN: 10643745     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-62703-308-4_2     Document Type: Article

References (218)

1. Fisher JW (2003) Erythropoietin: physiology and pharmacology update. Exp Biol Med (Maywood) 228: 1-14
2. Wu H, Liu X, Jaenisch R, Lodish HF (1995) Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell 83: 59-67
3. Lin CS, Lim SK, D'Agati V, Costantini F (1996) Differential effects of an erythropoietin receptor gene disruption on primitive and definitive erythropoiesis. Genes Dev 10: 154-164
4. Masuda S, Okano M, Yamagishi K, Nagao M, Ueda M, Sasaki R (1994) A novel site of erythropoietin production. Oxygendependent production in cultured rat astrocytes. J Biol Chem 269: 19488-19493
5. Marti HH, Wenger RH, Rivas LA, Straumann U, Digicaylioglu M, Henn V, Yonekawa Y, Bauer C, Gassmann M (1996) Erythropoietin gene expression in human, monkey and murine brain. Eur J Neurosci 8: 666-676
6. Bernaudin M, Marti HH, Roussel S, Divoux D, Nouvelot A, MacKenzie ET, Petit E (1999) A potential role for erythropoietin in focal permanent cerebral ischemia in mice. J Cereb Blood Flow Metab 19: 643-651
7. Li Y, Lu ZY, Ogle M, Wei L (2007) Erythropoietin prevents blood brain barrier damage induced by focal cerebral ischemia in mice. Neurochem Res 32: 2132-2141
8. Korbel S, Bittorf T, Siegl E, Kollner B (2004) Recombinant human erythropoietin induces proliferation and Ca(2+)-influx in specific leukocyte subpopulations of rainbow trout (Oncorhynchus mykiss) blood and head kidney cells. J Comp Physiol B 174: 121-128
9. Velly L, Pellegrini L, Guillet B, Bruder N, Pisano P (2010) Erythropoietin 2nd cerebral protection after acute injuries: a double-edged sword? Pharmacol Ther 128: 445-459
10. Vogel J, Kiessling I, Heinicke K, Stallmach T, Ossent P, Vogel O, Aulmann M, Frietsch T, Schmid-Schonbein H, Kuschinsky W, Gassmann M (2003) Transgenic mice overexpressing erythropoietin adapt to excessive erythrocytosis by regulating blood viscosity. Blood 102: 2278-2284
11. Grimm C, Wenzel A, Groszer M, Mayser H, Seeliger M, Samardzija M, Bauer C, Gassmann M, Reme CE (2002) HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration. Nat Med 8: 718-724
12. Junk AK, Mammis A, Savitz SI, Singh M, Roth S, Malhotra S, Rosenbaum PS, Cerami A, Brines M, Rosenbaum DM (2002) Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury. Proc Natl Acad Sci U S A 99: 10659-10664
13. Ribatti D, Vacca A, Roccaro AM, Crivellato E, Presta M (2003) Erythropoietin as an angiogenic factor. Eur J Clin Invest 33: 891-896
14. Soliz J, Joseph V, Soulage C, Becskei C, Vogel J, Pequignot JM, Ogunshola O, Gassmann M (2005) Erythropoietin regulates hypoxic ventilation in mice by interacting with brainstem and carotid bodies. J Physiol 568: 559-571
15. Soliz J, Gassmann M, Joseph V (2007) Soluble erythropoietin receptor is present in the mouse brain and is required for the ventilatory acclimatization to hypoxia. J Physiol 583: 329-336
16. Semenza GL, Nejfelt MK, Chi SM, Antonarakis SE (1991) Hypoxia-inducible nuclear factors bind to an enhancer element located 3 ¢ to the human erythropoietin gene. Proc Natl Acad Sci U S A 88: 5680-5684
17. Semenza GL, Wang GL (1992) A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 12: 5447-5454
18. Ema M, Taya S, Yokotani N, Sogawa K, Matsuda Y, Fujii-Kuriyama Y (1997) A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development. Proc Natl Acad Sci U S A 94: 4273-4278
19. Flamme I, Frohlich T, von Reutern M, Kappel A, Damert A, Risau W (1997) HRF, a putative basic helix-loop-helix-PAS-domain transcription factor is closely related to hypoxia-inducible factor-1 alpha and developmentally expressed in blood vessels. Mech Dev 63: 51-60
20. Tian H, McKnight SL, Russell DW (1997) Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev 11: 72-82
21. Morita M, Ohneda O, Yamashita T, Takahashi S, Suzuki N, Nakajima O, Kawauchi S, Ema M, Shibahara S, Udono T, Tomita K, Tamai M, Sogawa K, Yamamoto M, Fujii-Kuriyama Y (2003) HLF/HIF-2alpha is a key factor in retinopathy of prematurity in association with erythropoietin. EMBO J 22: 1134-1146
22. Warnecke C, Zaborowska Z, Kurreck J, Erdmann VA, Frei U, Wiesener M, Eckardt KU (2004) Differentiating the functional role of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha (EPAS-1) by the use of RNA interference: erythropoietin is a HIF-2alpha target gene in Hep3B and Kelly cells. FASEB J 18: 1462-1464
23. Chavez JC, Baranova O, Lin J, Pichiule P (2006) The transcriptional activator hypoxia inducible factor 2 (HIF-2/EPAS-1) regulates the oxygen-dependent expression of erythropoietin in cortical astrocytes. J Neurosci 26: 9471-9481
24. Kapitsinou PP, Liu Q, Unger TL, Rha J, Davidoff O, Keith B, Epstein JA, Moores SL, Erickson-Miller CL, Haase VH (2010) Hepatic HIF-2 regulates erythropoietic responses to hypoxia in renal anemia. Blood 116: 3039-3048
25. Loboda A, Jozkowicz A, Dulak J (2010) HIF-1 and HIF-2 transcription factors-similar but not identical. Mol Cells 29: 435-442
26. Hopfl G, Ogunshola O, Gassmann M (2003) Hypoxia and high altitude. The molecular response. Adv Exp Med Biol 543: 89-115
27. Fandrey J, Gassmann M (2009) Oxygen sensing and the activation of the hypoxia inducible factor 1 (HIF-1)-invited article. Adv Exp Med Biol 648: 197-206
28. Stiehl DP, Wirthner R, Koditz J, Spielmann P, Camenisch G, Wenger RH (2006) Increased prolyl 4-hydroxylase domain proteins compensate for decreased oxygen levels. Evidence for an autoregulatory oxygen-sensing system. J Biol Chem 281: 23482-23491
29. Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, Ratcliffe PJ (2001) Targeting of HIF-alpha to the von Hippel- Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292: 468-472
30. Webb JD, Coleman ML, Pugh CW (2009) Hypoxia, hypoxia-inducible factors (HIF), HIF hydroxylases and oxygen sensing. Cell Mol Life Sci 66: 3539-3554
31. Haase VH (2009) The VHL tumor suppressor: master regulator of HIF. Curr Pharm Des 15: 3895-3903
32. Lee-Huang S, Lin JJ, Kung HF, Huang PL, Lee L (1993) The human erythropoietin-encoding gene contains a CAAT box, TATA boxes and other transcriptional regulatory elements in its 5 ¢flanking region. Gene 128: 227-236
33. Blanchard KL, Acquaviva AM, Galson DL, Bunn HF (1992) Hypoxic induction of the human erythropoietin gene: cooperation between the promoter and enhancer, each of which contains steroid receptor response elements. Mol Cell Biol 12: 5373-5385
34. Imagawa S, Yamamoto M, Miura Y (1997) Negative regulation of the erythropoietin gene expression by the GATA transcription factors. Blood 89: 1430-1439
35. La Ferla K, Reimann C, Jelkmann W, Hellwig- Burgel T (2002) Inhibition of erythropoietin gene expression signaling involves the transcription factors GATA-2 and NF-kappaB. FASEB J 16: 1811-1813
36. Grasso G, Sfacteria A, Cerami A, Brines M (2004) Erythropoietin as a tissue-protective cytokine in brain injury: what do we know and where do we go? Neuroscientist 10: 93-98
37. Marti HH (2004) Erythropoietin and the hypoxic brain. J Exp Biol 207: 3233-3242
38. D'Andrea AD, Lodish HF, Wong GG (1989) Expression cloning of the murine erythropoietin receptor. Cell 57: 277-285
39. Jones SS, D'Andrea AD, Haines LL, Wong GG (1990) Human erythropoietin receptor: cloning, expression, and biologic characterization. Blood 76: 31-35
40. Anagnostou A, Liu Z, Steiner M, Chin K, Lee ES, Kessimian N, Noguchi CT (1994) Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci U S A 91: 3974-3978
41. Ogilvie M, Yu X, Nicolas-Metral V, Pulido SM, Liu C, Ruegg UT, Noguchi CT (2000) Erythropoietin stimulates proliferation and interferes with differentiation of myoblasts. J Biol Chem 275: 39754-39761
42. Shingo T, Sorokan ST, Shimazaki T, Weiss S (2001) Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells. J Neurosci 21: 9733-9743
43. Juul SE, Anderson DK, Li Y, Christensen RD (1998) Erythropoietin and erythropoietin receptor in the developing human central nervous system. Pediatr Res 43: 40-49
44. Bernaudin M, Bellail A, Marti HH, Yvon A, Vivien D, Duchatelle I, Mackenzie ET, Petit E (2000) Neurons and astrocytes express EPO mRNA: oxygen-sensing mechanisms that involve the redox-state of the brain. Glia 30: 271-278
45. Liu C, Shen K, Liu Z, Noguchi CT (1997) Regulated human erythropoietin receptor expression in mouse brain. J Biol Chem 272: 32395-32400
46. Digicaylioglu M, Bichet S, Marti HH, Wenger RH, Rivas LA, Bauer C, Gassmann M (1995) Localization of specific erythropoietin binding sites in defined areas of the mouse brain. Proc Natl Acad Sci U S A 92: 3717-3720
47. Ruifrok WP, de Boer RA, Westenbrink BD, van Veldhuisen DJ, van Gilst WH (2008) Erythropoietin in cardiac disease: new features of an old drug. Eur J Pharmacol 585: 270-277
48. Brines M, Cerami A (2006) Discovering erythropoietin's extra-hematopoietic functions: biology and clinical promise. Kidney Int 70: 246-250
49. Fenjves ES, Ochoa MS, Cabrera O, Mendez AJ, Kenyon NS, Inverardi L, Ricordi C (2003) Human, nonhuman primate, and rat pancreatic islets express erythropoietin receptors. Transplantation 75: 1356-1360
50. Yasuda Y, Masuda S, Chikuma M, Inoue K, Nagao M, Sasaki R (1998) Estrogendependent production of erythropoietin in uterus and its implication in uterine angiogenesis. J Biol Chem 273: 25381-25387
51. Constantinescu SN, Keren T, Socolovsky M, Nam H, Henis YI, Lodish HF (2001) Ligandindependent oligomerization of cell-surface erythropoietin receptor is mediated by the transmembrane domain. Proc Natl Acad Sci U S A 98: 4379-4384
52. Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, Ihle JN (1993) JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell 74: 227-236
53. Miura O, Nakamura N, Quelle FW, Witthuhn BA, Ihle JN, Aoki N (1994) Erythropoietin induces association of the JAK2 protein tyrosine kinase with the erythropoietin receptor in vivo. Blood 84: 1501-1507
54. Quelle FW, Wang D, Nosaka T, Thierfelder WE, Stravopodis D, Weinstein Y, Ihle JN (1996) Erythropoietin induces activation of Stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response. Mol Cell Biol 16: 1622-1631
55. Zhao W, Kitidis C, Fleming MD, Lodish HF, Ghaffari S (2006) Erythropoietin stimulates phosphorylation and activation of GATA-1 via the PI3-kinase/AKT signaling pathway. Blood 107: 907-915
56. Jelkmann W, Bohlius J, Hallek M, Sytkowski AJ (2008) The erythropoietin receptor in normal and cancer tissues. Crit Rev Oncol Hematol 67: 39-61
57. Socolovsky M, Nam H, Fleming MD, Haase VH, Brugnara C, Lodish HF (2001) Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts. Blood 98: 3261-3273
58. Bao H, Jacobs-Helber SM, Lawson AE, Penta K, Wickrema A, Sawyer ST (1999) Protein kinase B (c-Akt), phosphatidylinositol 3-kinase, and STAT5 are activated by erythropoietin (EPO) in HCD57 erythroid cells but are constitutively active in an EPOindependent, apoptosis-resistant subclone (HCD57-SREI cells). Blood 93: 3757-3773
59. Simon MC, Pevny L, Wiles MV, Keller G, Costantini F, Orkin SH (1992) Rescue of erythroid development in gene targeted GATA-1- mouse embryonic stem cells. Nat Genet 1: 92-98
60. Buck I, Morceau F, Cristofanon S, Heintz C, Chateauvieux S, Reuter S, Dicato M, Diederich M (2008) Tumor necrosis factor alpha inhibits erythroid differentiation in human erythropoietin-dependent cells involving p38 MAPK pathway, GATA-1 and FOG-1 downregulation and GATA-2 upregulation. Biochem Pharmacol 76: 1229-1239
61. Ohneda K, Yamamoto M (2002) Roles of hematopoietic transcription factors GATA-1 and GATA-2 in the development of red blood cell lineage. Acta Haematol 108: 237-245
62. Chong ZZ, Kang JQ, Maiese K (2003) Apaf- 1, Bcl-xL, cytochrome c, and caspase-9 form the critical elements for cerebral vascular protection by erythropoietin. J Cereb Blood Flow Metab 23: 320-330
63. Szenajch J, Wcislo G, Jeong JY, Szczylik C, Feldman L (2010) The role of erythropoietin and its receptor in growth, survival and therapeutic response of human tumor cells From clinic to bench-a critical review. Biochim Biophys Acta 1806: 82-95
64. Mahmud DL, G-Amlak M, Deb DK, Platanias LC, Uddin S, Wickrema A (2002) Phosphorylation of forkhead transcription factors by erythropoietin and stem cell factor prevents acetylation and their interaction with coactivator p300 in erythroid progenitor cells. Oncogene 21: 1556-1562
65. Chong ZZ, Maiese K (2007) Erythropoietin involves the phosphatidylinositol 3-kinase pathway, 14-3-3 protein and FOXO3a nuclear trafficking to preserve endothelial cell integrity. Br J Pharmacol 150: 839-850
66. Nagata Y, Todokoro K (1999) Requirement of activation of JNK and p38 for environmental stress-induced erythroid differentiation and apoptosis and of inhibition of ERK for apoptosis. Blood 94: 853-863
67. Nagata Y, Kiefer F, Watanabe T, Todokoro K (1999) Activation of hematopoietic progenitor kinase-1 by erythropoietin. Blood 93: 3347-3354
68. Kolbus A, Pilat S, Husak Z, Deiner EM, Stengl G, Beug H, Baccarini M (2002) Raf-1 antagonizes erythroid differentiation by restraining caspase activation. J Exp Med 196: 1347-1353
69. Uddin S, Ah-Kang J, Ulaszek J, Mahmud D, Wickrema A (2004) Differentiation stagespecific activation of p38 mitogen-activated protein kinase isoforms in primary human erythroid cells. Proc Natl Acad Sci U S A 101: 147-152
70. Jacobs-Helber SM, Ryan JJ, Sawyer ST (2000) JNK and p38 are activated by erythropoietin (EPO) but are not induced in apoptosis following EPO withdrawal in EPO-dependent HCD57 cells. Blood 96: 933-940
71. Nagao M, Masuda S, Abe S, Ueda M, Sasaki R (1992) Production and ligand-binding characteristics of the soluble form of murine erythropoietin receptor. Biochem Biophys Res Commun 188: 888-897
72. Fujita M, Takahashi R, Liang P, Saya H, Ashoori F, Tachi M, Kitazawa S, Maeda S (1997) Role of alternative splicing of the rat erythropoietin receptor gene in normal and erythroleukemia cells. Leukemia 11(Suppl 3): 444-445
73. Chikuma M, Masuda S, Kobayashi T, Nagao M, Sasaki R (2000) Tissue-specific regulation of erythropoietin production in the murine kidney, brain, and uterus. Am J Physiol Endocrinol Metab 279:E1242-E1248
74. Masuda S, Nagao M, Takahata K, Konishi Y, Gallyas F Jr, Tabira T, Sasaki R (1993) Functional erythropoietin receptor of the cells with neural characteristics. Comparison with receptor properties of erythroid cells. J Biol Chem 268: 11208-11216
75. Brines M, Cerami A (2011) The receptor that tames the innate immune response. Mol Med 18: 486-496
76. Brines M, Cerami A (2005) Emerging biological roles for erythropoietin in the nervous system. Nat Rev Neurosci 6: 484-494
77. Sinclair AM, Coxon A, McCaffery I, Kaufman S, Paweletz K, Liu L, Busse L, Swift S, Elliott S, Begley CG (2010) Functional erythropoietin receptor is undetectable in endothelial, cardiac, neuronal, and renal cells. Blood 115: 4264-4272
78. Ghezzi P, Bernaudin M, Bianchi R, Blomgren K, Brines M, Campana W, Cavaletti G, Cerami A, Chopp M, Coleman T, Digicaylioglu M, Ehrenreich H, Erbayraktar S, Erbayraktar Z, Gassmann M, Genc S, Gokmen N, Grasso G, Juul S, Lipton SA, Hand CC, Latini R, Lauria G, Leist M, Newton SS, Petit E, Probert L, Sfacteria A, Siren AL, Talan M, Thiemermann C, Westenbrink D, Yaqoob M, Zhu C (2010) Erythropoietin: not just about erythropoiesis. Lancet 375:2142
79. Brines M, Grasso G, Fiordaliso F, Sfacteria A, Ghezzi P, Fratelli M, Latini R, Xie QW, Smart J, Su-Rick CJ, Pobre E, Diaz D, Gomez D, Hand C, Coleman T, Cerami A (2004) Erythropoietin mediates tissue protection through an erythropoietin and common betasubunit heteroreceptor. Proc Natl Acad Sci U S A 101: 14907-14912
80. Swartjes M, Morariu A, Niesters M, Brines M, Cerami A, Aarts L, Dahan A (2011) ARA290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain: an experimental study in rats and beta-common receptor knockout mice. Anesthesiology 115: 1084-1092
81. Su KH, Shyue SK, Kou YR, Ching LC, Chiang AN, Yu YB, Chen CY, Pan CC, Lee TS (2011) beta Common receptor integrates the erythropoietin signaling in activation of endothelial nitric oxide synthase. J Cell Physiol 226: 3330-3339
82. Teng R, Gavrilova O, Suzuki N, Chanturiya T, Schimel D, Hugendubler L, Mammen S, Yver DR, Cushman SW, Mueller E, Yamamoto M, Hsu LL, Noguchi CT (2011) Disrupted erythropoietin signalling promotes obesity and alters hypothalamus proopiomelanocortin production. Nat Commun 2:520
83. Teng R, Calvert JW, Sibmooh N, Piknova B, Suzuki N, Sun J, Martinez K, Yamamoto M, Schechter AN, Lefer DJ, Noguchi CT (2011) Acute erythropoietin cardioprotection is mediated by endothelial response. Basic Res Cardiol 106: 343-354
84. Xiong Y, Mahmood A, Qu C, Kazmi H, Zhang ZG, Noguchi CT, Schallert T, Chopp M (2010) Erythropoietin improves histological and functional outcomes after traumatic brain injury in mice in the absence of the neural erythropoietin receptor. J Neurotrauma 27: 205-215
85. Tsai PT, Ohab JJ, Kertesz N, Groszer M, Matter C, Gao J, Liu X, Wu H, Carmichael ST (2006) A critical role of erythropoietin receptor in neurogenesis and post-stroke recovery. J Neurosci 26: 1269-1274
86. Nagai A, Nakagawa E, Choi HB, Hatori K, Kobayashi S, Kim SU (2001) Erythropoietin and erythropoietin receptors in human CNS neurons, astrocytes, microglia, and oligodendrocytes grown in culture. J Neuropathol Exp Neurol 60: 386-392
87. Brines ML, Ghezzi P, Keenan S, Agnello D, de Lanerolle NC, Cerami C, Itri LM, Cerami A (2000) Erythropoietin crosses the blood- brain barrier to protect against experimental brain injury. Proc Natl Acad Sci U S A 97: 10526-10531
88. Ruscher K, Freyer D, Karsch M, Isaev N, Megow D, Sawitzki B, Priller J, Dirnagl U, Meisel A (2002) Erythropoietin is a paracrine mediator of ischemic tolerance in the brain: evidence from an in vitro model. J Neurosci 22: 10291-10301
89. Chong ZZ, Kang JQ, Maiese K (2002) Hematopoietic factor erythropoietin fosters neuroprotection through novel signal transduction cascades. J Cereb Blood Flow Metab 22: 503-514
90. Liu R, Suzuki A, Guo Z, Mizuno Y, Urabe T (2006) Intrinsic and extrinsic erythropoietin enhances neuroprotection against ischemia and reperfusion injury in vitro. J Neurochem 96: 1101-1110
91. Lewczuk P, Hasselblatt M, Kamrowski-Kruck H, Heyer A, Unzicker C, Siren AL, Ehrenreich H (2000) Survival of hippocampal neurons in culture upon hypoxia: effect of erythropoietin. Neuroreport 11: 3485-3488
92. Koshimura K, Murakami Y, Sohmiya M, Tanaka J, Kato Y (1999) Effects of erythropoietin on neuronal activity. J Neurochem 72: 2565-2572
93. Morishita E, Narita H, Nishida M, Kawashima N, Yamagishi K, Masuda S, Nagao M, Hatta H, Sasaki R (1996) Anti-erythropoietin receptor monoclonal antibody: epitope mapping, quantification of the soluble receptor, and detection of the solubilized transmembrane receptor and the receptor-expressing cells. Blood 88: 465-471
94. Shang Y, Wu Y, Yao S, Wang X, Feng D, Yang W (2007) Protective effect of erythropoietin against ketamine-induced apoptosis in cultured rat cortical neurons: involvement of PI3K/Akt and GSK-3 beta pathway. Apoptosis 12: 2187-2195
95. Yoo JY, Won YJ, Lee JH, Kim JU, Sung IY, Hwang SJ, Kim MJ, Hong HN (2009) Neuroprotective effects of erythropoietin posttreatment against kainate-induced excitotoxicity in mixed spinal cultures. J Neurosci Res 87: 150-163
96. Um M, Gross AW, Lodish HF (2007) A "classical" homodimeric erythropoietin receptor is essential for the antiapoptotic effects of erythropoietin on differentiated neuroblastoma SH-SY5Y and pheochromocytoma PC-12 cells. Cell Signal 19: 634-645
97. Zhang L, Chopp M, Zhang RL, Wang L, Zhang J, Wang Y, Toh Y, Santra M, Lu M, Zhang ZG (2010) Erythropoietin amplifies stroke-induced oligodendrogenesis in the rat. PLoS One 5:e11016
98. Cho YK, Kim G, Park S, Sim JH, Won YJ, Hwang CH, Yoo JY, Hong HN (2012) Erythropoietin promotes oligodendrogenesis and myelin repair following lysolecithininduced injury in spinal cord slice culture. Biochem Biophys Res Commun 417: 753-759
99. Genc K, Genc S, Baskin H, Semin I (2006) Erythropoietin decreases cytotoxicity and nitric oxide formation induced by inflammatory stimuli in rat oligodendrocytes. Physiol Res 55: 33-38
100. Digicaylioglu M, Lipton SA (2001) Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Nature 412: 641-647
101. Marrero MB, Venema RC, Ma H, Ling BN, Eaton DC (1998) Erythropoietin receptoroperated Ca2+ channels: activation by phospholipase C-gamma 1. Kidney Int 53: 1259-1268
102. Kawakami M, Iwasaki S, Sato K, Takahashi M (2000) Erythropoietin inhibits calciuminduced neurotransmitter release from clonal neuronal cells. Biochem Biophys Res Commun 279: 293-297
103. Souvenir R, Fathali N, Ostrowski RP, Lekic T, Zhang JH, Tang J (2011) Tissue inhibitor of matrix metalloproteinase-1 mediates erythropoietin- induced neuroprotection in hypoxia ischemia. Neurobiol Dis 44: 28-37
104. Chen ZY, Wang L, Asavaritkrai P, Noguchi CT (2010) Up-regulation of erythropoietin receptor by nitric oxide mediates hypoxia preconditioning. J Neurosci Res 88: 3180-3188
105. Keswani SC, Bosch-Marce M, Reed N, Fischer A, Semenza GL, Hoke A (2011) Nitric oxide prevents axonal degeneration by inducing HIF- 1-dependent expression of erythropoietin. Proc Natl Acad Sci U S A 108: 4986-4990
106. Belayev L, Saul I, Busto R, Danielyan K, Vigdorchik A, Khoutorova L, Ginsberg MD (2005) Albumin treatment reduces neurological deficit and protects blood-brain barrier integrity after acute intracortical hematoma in the rat. Stroke 36: 326-331
107. Siren AL, Knerlich F, Poser W, Gleiter CH, Bruck W, Ehrenreich H (2001) Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain. Acta Neuropathol 101: 271-276
108. Villa P, Bigini P, Mennini T, Agnello D, Laragione T, Cagnotto A, Viviani B, Marinovich M, Cerami A, Coleman TR, Brines M, Ghezzi P (2003) Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. J Exp Med 198: 971-975
109. Ehrenreich H, Bartels C, Sargin D, Stawicki S, Krampe H (2008) Recombinant human erythropoietin in the treatment of human brain disease: focus on cognition. J Ren Nutr 18: 146-153
110. Wang CH, Liang CL, Huang LT, Liu JK, Hung PH, Sun A, Hung KS (2004) Single intravenous injection of naked plasmid DNA encoding erythropoietin provides neuroprotection in hypoxia-ischemia rats. Biochem Biophys Res Commun 314: 1064-1071
111. Malhotra S, Savitz SI, Ocava L, Rosenbaum DM (2006) Ischemic preconditioning is mediated by erythropoietin through PI-3 kinase signaling in an animal model of transient ischemic attack. J Neurosci Res 83: 19-27
112. Prass K, Scharff A, Ruscher K, Lowl D, Muselmann C, Victorov I, Kapinya K, Dirnagl U, Meisel A (2003) Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin. Stroke 34: 1981-1986
113. Iwai M, Stetler RA, Xing J, Hu X, Gao Y, Zhang W, Chen J, Cao G (2010) Enhanced oligodendrogenesis and recovery of neurological function by erythropoietin after neonatal hypoxic/ischemic brain injury. Stroke 41: 1032-1037
114. McPherson RJ, Juul SE (2010) Erythropoietin for infants with hypoxic-ischemic encephalopathy. Curr Opin Pediatr 22: 139-145
115. Kumral A, Tuzun F, Oner MG, Genc S, Duman N, Ozkan H (2011) Erythropoietin in neonatal brain protection: the past, the present and the future. Brain Dev 33: 632-643
116. Mammis A, McIntosh TK, Maniker AH (2009) Erythropoietin as a neuroprotective agent in traumatic brain injury review. Surg Neurol 71:527-531, discussion 531
117. Agnello D, Bigini P, Villa P, Mennini T, Cerami A, Brines ML, Ghezzi P (2002) Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis. Brain Res 952: 128-134
118. Zhang J, Li Y, Cui Y, Chen J, Lu M, Elias SB, Chopp M (2005) Erythropoietin treatment improves neurological functional recovery in EAE mice. Brain Res 1034: 34-39
119. Celik M, Gokmen N, Erbayraktar S, Akhisaroglu M, Konakc S, Ulukus C, Genc S, Genc K, Sagiroglu E, Cerami A, Brines M (2002) Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Proc Natl Acad Sci U S A 99: 2258-2263
120. Gorio A, Gokmen N, Erbayraktar S, Yilmaz O, Madaschi L, Cichetti C, Di Giulio AM, Vardar E, Cerami A, Brines M (2002) Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. Proc Natl Acad Sci U S A 99: 9450-9455
121. Kilic E, Kilic U, Soliz J, Bassetti CL, Gassmann M, Hermann DM (2005) Brain-derived erythropoietin protects from focal cerebral ischemia by dual activation of ERK-1/-2 and Akt pathways. FASEB J 19: 2026-2028
122. Sola A, Wen TC, Hamrick SE, Ferriero DM (2005) Potential for protection and repair following injury to the developing brain: a role for erythropoietin? Pediatr Res 57: 110R-117R
123. Viviani B, Bartesaghi S, Corsini E, Villa P, Ghezzi P, Garau A, Galli CL, Marinovich M (2005) Erythropoietin protects primary hippocampal neurons increasing the expression of brain-derived neurotrophic factor. J Neurochem 93: 412-421
124. Weishaupt JH, Rohde G, Polking E, Siren AL, Ehrenreich H, Bahr M (2004) Effect of erythropoietin axotomy-induced apoptosis in rat retinal ganglion cells. Invest Ophthalmol Vis Sci 45: 1514-1522
125. Shen J, Wu Y, Xu JY, Zhang J, Sinclair SH, Yanoff M, Xu G, Li W, Xu GT (2010) ERKand Akt-dependent neuroprotection by erythropoietin (EPO) against glyoxal-AGEs via modulation of Bcl-xL, Bax, and BAD. Invest Ophthalmol Vis Sci 51: 35-46
126. Grimm C, Wenzel A, Stanescu D, Samardzija M, Hotop S, Groszer M, Naash M, Gassmann M, Reme C (2004) Constitutive overexpression of human erythropoietin protects the mouse retina against induced but not inherited retinal degeneration. J Neurosci 24: 5651-5658
127. Konishi Y, Chui DH, Hirose H, Kunishita T, Tabira T (1993) Trophic effect of erythropoietin and other hematopoietic factors on central cholinergic neurons in vitro and in vivo. Brain Res 609: 29-35
128. Bocker-Meffert S, Rosenstiel P, Rohl C, Warneke N, Held-Feindt J, Sievers J, Lucius R (2002) Erythropoietin and VEGF promote neural outgrowth from retinal explants in postnatal rats. Invest Ophthalmol Vis Sci 43: 2021-2026
129. Kretz A, Happold CJ, Marticke JK, Isenmann S (2005) Erythropoietin promotes regeneration of adult CNS neurons via Jak2/Stat3 and PI3K/AKT pathway activation. Mol Cell Neurosci 29: 569-579
130. Ehrenreich H, Hasselblatt M, Dembowski C, Cepek L, Lewczuk P, Stiefel M, Rustenbeck HH, Breiter N, Jacob S, Knerlich F, Bohn M, Poser W, Ruther E, Kochen M, Gefeller O, Gleiter C, Wessel TC, De Ryck M, Itri L, Prange H, Cerami A, Brines M, Siren AL (2002) Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 8: 495-505
131. Ehrenreich H, Weissenborn K, Prange H, Schneider D, Weimar C, Wartenberg K, Schellinger PD, Bohn M, Becker H, Wegrzyn M, Jahnig P, Herrmann M, Knauth M, Bahr M, Heide W, Wagner A, Schwab S, Reichmann H, Schwendemann G, Dengler R, Kastrup A, Bartels C (2009) Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke 40:e647-e656
132. Wustenberg T, Begemann M, Bartels C, Gefeller O, Stawicki S, Hinze-Selch D, Mohr A, Falkai P, Aldenhoff JB, Knauth M, Nave KA, Ehrenreich H (2011) Recombinant human erythropoietin delays loss of gray matter in chronic schizophrenia. Mol Psychiatry 16(26-36):21
133. Miskowiak K, O'Sullivan U, Harmer CJ (2007) Erythropoietin reduces neural and cognitive processing of fear in human models of antidepressant drug action. Biol Psychiatry 62: 1244-1250
134. Ehrenreich H, Fischer B, Norra C, Schellenberger F, Stender N, Stiefel M, Siren AL, Paulus W, Nave KA, Gold R, Bartels C (2007) Exploring recombinant human erythropoietin in chronic progressive multiple sclerosis. Brain 130: 2577-2588
135. Tseng MY, Hutchinson PJ, Richards HK, Czosnyka M, Pickard JD, Erber WN, Brown S, Kirkpatrick PJ (2009) Acute systemic erythropoietin therapy to reduce delayed ischemic deficits following aneurysmal subarachnoid hemorrhage: a Phase II randomized, doubleblind, placebo-controlled trial. Clinical article. J Neurosurg 111: 171-180
136. Nirula R, Diaz-Arrastia R, Brasel K, Weigelt JA, Waxman K (2010) Safety and efficacy of erythropoietin in traumatic brain injury patients: a pilot randomized trial. Crit Care Res Pract pii:209848
137. Asaumi Y, Kagaya Y, Takeda M, Yamaguchi N, Tada H, Ito K, Ohta J, Shiroto T, Shirato K, Minegishi N, Shimokawa H (2007) Protective role of endogenous erythropoietin system in nonhematopoietic cells against pressure overload- induced left ventricular dysfunction in mice. Circulation 115: 2022-2032
138. Wu H, Lee SH, Gao J, Liu X, Iruela-Arispe ML (1999) Inactivation of erythropoietin leads to defects in cardiac morphogenesis. Development 126: 3597-3605
139. Suzuki N, Ohneda O, Takahashi S, Higuchi M, Mukai HY, Nakahata T, Imagawa S, Yamamoto M (2002) Erythroid-specific expression of the erythropoietin receptor rescued its null mutant mice from lethality. Blood 100: 2279-2288
140. Stuckmann I, Evans S, Lassar AB (2003) Erythropoietin and retinoic acid, secreted from the epicardium, are required for cardiac myocyte proliferation. Dev Biol 255: 334-349
141. Hefer D, Yi T, Selby DE, Fishbaugher DE, Tremble SM, Begin KJ, Gogo P, Lewinter MM, Meyer M, Palmer BM, Vanburen P (2012) Erythropoietin induces positive inotropic and lusitropic effects in murine and human myocardium. J Mol Cell Cardiol 52: 256-263
142. Kaygisiz Z, Erkasap N, Yazihan N, Sayar K, Ataoglu H, Uyar R, Ikizler M (2006) Erythropoietin changes contractility, cAMP, and nitrite levels of isolated rat hearts. J Physiol Sci 56: 247-251
143. Hanlon PR, Fu P, Wright GL, Steenbergen C, Arcasoy MO, Murphy E (2005) Mechanisms of erythropoietin-mediated cardioprotection during ischemia-reperfusion injury: role of protein kinase C and phosphatidylinositol 3-kinase signaling. FASEB J 19: 1323-1325
144. Wright GL, Hanlon P, Amin K, Steenbergen C, Murphy E, Arcasoy MO (2004) Erythropoietin receptor expression in adult rat cardiomyocytes is associated with an acute cardioprotective effect for recombinant erythropoietin during ischemia-reperfusion injury. FASEB J 18: 1031-1033
145. Salisch S, Klar M, Thurisch B, Bungert J, Dame C (2011) Gata4 and Sp1 regulate expression of the erythropoietin receptor in cardiomyocytes. J Cell Mol Med 15: 1963-1972
146. Depping R, Kawakami K, Ocker H, Wagner JM, Heringlake M, Noetzold A, Sievers HH, Wagner KF (2005) Expression of the erythropoietin receptor in human heart. J Thorac Cardiovasc Surg 130: 877-878
147. Mihov D, Bogdanov N, Grenacher B, Gassmann M, Zund G, Bogdanova A, Tavakoli R (2009) Erythropoietin protects from reperfusion- induced myocardial injury by enhancing coronary endothelial nitric oxide production. Eur J Cardiothorac Surg 35:839-846, discussion 846
148. Parsa CJ, Kim J, Riel RU, Pascal LS, Thompson RB, Petrofski JA, Matsumoto A, Stamler JS, Koch WJ (2004) Cardioprotective effects of erythropoietin in the reperfused ischemic heart: a potential role for cardiacfibroblasts. J Biol Chem 279: 20655-20662
149. Moon C, Krawczyk M, Paik D, Coleman T, Brines M, Juhaszova M, Sollott SJ, Lakatta EG, Talan MI (2006) Erythropoietin, modified to not stimulate red blood cell production, retains its cardioprotective properties. J Pharmacol Exp Ther 316: 999-1005
150. Ahmet I, Tae HJ, Juhaszova M, Riordon DR, Boheler KR, Sollott SJ, Brines M, Cerami A, Lakatta EG, Talan MI (2011) A small nonerythropoietic helix B surface peptide based upon erythropoietin structure is cardioprotective against ischemic myocardial damage. Mol Med 17: 194-200
151. Chin K, Oda N, Shen K, Noguchi CT (1995) Regulation of transcription of the human erythropoietin receptor gene by proteins binding to GATA-1 and Sp1 motifs. Nucleic Acids Res 23: 3041-3049
152. Kirschner KM, Hagen P, Hussels CS, Ballmaier M, Scholz H, Dame C (2008) The Wilms' tumor suppressor Wt1 activates transcription of the erythropoietin receptor in hematopoietic progenitor cells. FASEB J 22: 2690-2701
153. Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, von Gise A, Ikeda S, Chien KR, Pu WT (2008) Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 454: 109-113
154. Chu CY, Cheng CH, Chen GD, Chen YC, Hung CC, Huang KY, Huang CJ (2007) The zebrafish erythropoietin: functional identification and biochemical characterization. FEBS Lett 581: 4265-4271
155. Lin JS, Chen YS, Chiang HS, Ma MC (2008) Hypoxic preconditioning protects rat hearts against ischaemia-reperfusion injury: role of erythropoietin on progenitor cell mobilization. J Physiol 586: 5757-5769
156. Piuhola J, Kerkela R, Keenan JI, Hampton MB, Richards AM, Pemberton CJ (2008) Direct cardiac actions of erythropoietin (EPO): effects on cardiac contractility, BNP secretion and ischaemia/reperfusion injury. Clin Sci (Lond) 114: 293-304
157. Li Y, Takemura G, Okada H, Miyata S, Maruyama R, Li L, Higuchi M, Minatoguchi S, Fujiwara T, Fujiwara H (2006) Reduction of inflammatory cytokine expression and oxidative damage by erythropoietin in chronic heart failure. Cardiovasc Res 71: 684-694
158. Fu P, Arcasoy MO (2007) Erythropoietin protects cardiac myocytes against anthracycline- induced apoptosis. Biochem Biophys Res Commun 354: 372-378
159. Burger D, Lei M, Geoghegan-Morphet N, Lu X, Xenocostas A, Feng Q (2006) Erythropoietin protects cardiomyocytes from apoptosis via upregulation of endothelial nitric oxide synthase. Cardiovasc Res 72: 51-59
160. Fliser D, Bahlmann FH, deGroot K, Haller H (2006) Mechanisms of disease: erythropoietin- an old hormone with a new mission? Nat Clin Pract Cardiovasc Med 3: 563-572
161. Vogiatzi G, Briasoulis A, Tousoulis D, Papageorgiou N, Stefanadis C (2010) Is there a role for erythropoietin in cardiovascular disease? Expert Opin Biol Ther 10: 251-264
162. Burger D, Xenocostas A, Feng QP (2009) Molecular basis of cardioprotection by erythropoietin. Curr Mol Pharmacol 2: 56-69
163. Mihov D, Vogel J, Gassmann M, Bogdanova A (2009) Erythropoietin activates nitric oxide synthase in murine erythrocytes. Am J Physiol Cell Physiol 297:C378-C388
164. Li H, Wallerath T, Munzel T, Forstermann U (2002) Regulation of endothelial-type NO synthase expression in pathophysiology and in response to drugs. Nitric Oxide 7: 149-164
165. Ziolo MT, Kohr MJ, Wang H (2008) Nitric oxide signaling and the regulation of myocardial function. J Mol Cell Cardiol 45: 625-632
166. Joyeux-Faure M, Ramond A, Beguin PC, Belaidi E, Godin-Ribuot D, Ribuot C (2006) Early pharmacological preconditioning by erythropoietin mediated by inducible NOS and mitochondrial ATP-dependent potassium channels in the rat heart. Fundam Clin Pharmacol 20: 51-56
167. Baker JE, Kozik D, Hsu AK, Fu X, Tweddell JS, Gross GJ (2007) Darbepoetin alfa protects the rat heart against infarction: dose- response, phase of action, and mechanisms. J Cardiovasc Pharmacol 49: 337-345
168. Carraway MS, Suliman HB, Jones WS, Chen CW, Babiker A, Piantadosi CA (2010) Erythropoietin activates mitochondrial biogenesis and couples red cell mass to mitochondrial mass in the heart. Circ Res 106: 1722-1730
169. Cook SA, Matsui T, Li L, Rosenzweig A (2002) Transcriptional effects of chronic Akt activation in the heart. J Biol Chem 277: 22528-22533
170. Krishnan J, Suter M, Windak R, Krebs T, Felley A, Montessuit C, Tokarska-Schlattner M, Aasum E, Bogdanova A, Perriard E, Perriard JC, Larsen T, Pedrazzini T, Krek W (2009) Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy. Cell Metab 9: 512-524
171. Matsui T, Tao J, del Monte F, Lee KH, Li L, Picard M, Force TL, Franke TF, Hajjar RJ, Rosenzweig A (2001) Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation 104: 330-335
172. Gross AW, Lodish HF (2006) Cellular trafficking and degradation of erythropoietin and novel erythropoiesis stimulating protein (NESP). J Biol Chem 281: 2024-2032
173. Moon C, Krawczyk M, Paik D, Lakatta EG, Talan MI (2005) Cardioprotection by recombinant human erythropoietin following acute experimental myocardial infarction: dose response and therapeutic window. Cardiovasc Drugs Ther 19: 243-250
174. Jelkmann W, Wagner K (2004) Beneficial and ominous aspects of the pleiotropic action of erythropoietin. Ann Hematol 83: 673-686
175. Andreotti F, Agati L, Conti E, Santucci E, Rio T, Tarantino F, Natale L, Berardi D, Mattatelli A, Musumeci B, Bonomo L, Volpe M, Crea F, Autore C (2009) Update on phase II studies of erythropoietin in acute myocardial infarction. Rationale and design of Exogenous erythroPoietin in Acute Myocardial Infarction: New Outlook aNd Dose Association Study (EPAMINONDAS). J Thromb Thrombolysis 28: 489-495
176. Kang HJ, Kim HS (2008) G-CSF- and erythropoietin- based cell therapy: a promising strategy for angiomyogenesis in myocardial infarction. Expert Rev Cardiovasc Ther 6: 703-713
177. McMurray JJ, Uno H, Jarolim P, Desai AS, de Zeeuw D, Eckardt KU, Ivanovich P, Levey AS, Lewis EF, McGill JB, Parfrey P, Parving HH, Toto RM, Solomon SD, Pfeffer MA (2011) Predictors of fatal and nonfatal cardiovascular events in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia: an analysis of the Trial to Reduce cardiovascular Events with Aranesp (darbepoetin-alfa) Therapy (TREAT). Am Heart J 162(748-755):e743
178. Joyeux-Faure M, Durand M, Bedague D, Protar D, Incagnoli P, Paris A, Ribuot C, Levy P, Chavanon O (2011) Evaluation of the effect of one large dose of erythropoietin against cardiac and cerebral ischemic injury occurring during cardiac surgery with cardiopulmonary bypass: a randomized double-blind placebo-controlled pilot study. Fundam Clin Pharmacol 26: 761-770
179. van der Meer P, van Veldhuisen DJ (2011) Acute coronary syndromes: the unfulfilled promise of erythropoietin in patients with MI. Nat Rev Cardiol 8: 425-426
180. Moens AL, Kietadisorn R, Lin JY, Kass D (2011) Targeting endothelial and myocardial dysfunction with tetrahydrobiopterin. J Mol Cell Cardiol 51: 559-563
181. Forstermann U, Sessa WC (2011) Nitric oxide synthases: regulation and function. Eur Heart J 33: 829-837
182. Karbach S, Simon A, Slenzka A, Jaenecke I, Habermeier A, Martine U, Forstermann U, Closs EI (2011) Relative contribution of different L -arginine sources to the substrate supply of endothelial nitric oxide synthase. J Mol Cell Cardiol 51: 855-861
183. Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87: 315-424
184. Otani H (2009) The role of nitric oxide in myocardial repair and remodeling. Antioxid Redox Signal 11: 1913-1928
185. Hein TW, Zhang C, Wang W, Chang CI, Thengchaisri N, Kuo L (2003) Ischemiareperfusion selectively impairs nitric oxidemediated dilation in coronary arterioles: counteracting role of arginase. FASEB J 17: 2328-2330
186. Dweik RA (2005) Nitric oxide, hypoxia, and superoxide: the good, the bad, and the ugly! Thorax 60: 265-267
187. Ryou MG, Flaherty DC, Hoxha B, Sun J, Gurji H, Rodriguez S, Bell G, Olivencia- Yurvati AH, Mallet RT (2009) Pyruvatefortified cardioplegia evokes myocardial erythropoietin signaling in swine undergoing cardiopulmonary bypass. Am J Physiol Heart Circ Physiol 297:H1914-H1922
188. Allegra V, Mengozzi G, Martimbianco L, Vasile A (1996) Early and late effects of erythropoietin on glucose metabolism in maintenance hemodialysis patients. Am J Nephrol 16: 304-308
189. Mak RH (1996) Correction of anemia by erythropoietin reverses insulin resistance and hyperinsulinemia in uremia. Am J Physiol 270:F839-F844
190. Tuzcu A, Bahceci M, Yilmaz E, Bahceci S, Tuzcu S (2004) The comparison of insulin sensitivity in non-diabetic hemodialysis patients treated with and without recombinant human erythropoietin. Horm Metab Res 36: 716-720
191. Fenjves ES, Ochoa MS, Gay-Rabinstein C, Molano RD, Pileggi A, Mendez AJ, Inverardi L, Ricordi C (2004) Adenoviral gene transfer of erythropoietin confers cytoprotection to isolated pancreatic islets. Transplantation 77: 13-18
192. Katz O, Stuible M, Golishevski N, Lifshitz L, Tremblay ML, Gassmann M, Mittelman M, Neumann D (2010) Erythropoietin treatment leads to reduced blood glucose levels and body mass: insights from murine models. J Endocrinol 205: 87-95
193. Shuai H, Zhang J, Xie J, Zhang M, Yu Y, Zhang L (2011) Erythropoietin protects pancreatic beta-cell line NIT-1 cells against cytokine-induced apoptosis via phosphatidylinositol 3-kinase/Akt signaling. Endocr Res 36: 25-34
194. Choi D, Schroer SA, Lu SY, Wang L, Wu X, Liu Y, Zhang Y, Gaisano HY, Wagner KU, Wu H, Retnakaran R, Woo M (2010) Erythropoietin protects against diabetes through direct effects on pancreatic beta cells. J Exp Med 207: 2831-2842
195. Scully MS, Ort TA, James IE, Bugelski PJ, Makropoulos DA, Deutsch HA, Pieterman EJ, van den Hoek AM, Havekes LM, Dubell WH, Wertheimer JD, Picha KM (2011) A novel EPO receptor agonist improves glucose tolerance via glucose uptake in skeletal muscle in a mouse model of diabetes. Exp Diabetes Res 2011:910159
196. Noguchi CT, Wang L, Rogers HM, Teng R, Jia Y (2008) Survival and proliferative roles of erythropoietin beyond the erythroid lineage. Expert Rev Mol Med 10:e36
197. Masuda H, Asahara T (2003) Post-natal endothelial progenitor cells for neovascularization in tissue regeneration. Cardiovasc Res 58: 390-398
198. Urbich C, Dimmeler S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95: 343-353
199. Carlini RG, Alonzo EJ, Dominguez J, Blanca I, Weisinger JR, Rothstein M, Bellorin-Font E (1999) Effect of recombinant human erythropoietin on endothelial cell apoptosis. Kidney Int 55: 546-553
200. Carlini RG, Reyes AA, Rothstein M (1995) Recombinant human erythropoietin stimulates angiogenesis in vitro. Kidney Int 47: 740-745
201. Ribatti D, Presta M, Vacca A, Ria R, Giuliani R, Dell'Era P, Nico B, Roncali L, Dammacco F (1999) Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood 93: 2627-2636
202. Bahlmann FH, DeGroot K, Duckert T, Niemczyk E, Bahlmann E, Boehm SM, Haller H, Fliser D (2003) Endothelial progenitor cell proliferation and differentiation is regulated by erythropoietin. Kidney Int 64: 1648-1652
203. Bahlmann FH, De Groot K, Spandau JM, Landry AL, Hertel B, Duckert T, Boehm SM, Menne J, Haller H, Fliser D (2004) Erythropoietin regulates endothelial progenitor cells. Blood 103: 921-926
204. Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C, Mildner- Rihm C, Martin H, Zeiher AM, Dimmeler S (2003) Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 102: 1340-1346
205. Santhanam AV, d'Uscio LV, Peterson TE, Katusic ZS (2008) Activation of endothelial nitric oxide synthase is critical for erythropoietin- induced mobilization of progenitor cells. Peptides 29: 1451-1455
206. Westenbrink BD, Lipsic E, van der Meer P, van der Harst P, Oeseburg H, Du Marchie Sarvaas GJ, Koster J, Voors AA, van Veldhuisen DJ, van Gilst WH, Schoemaker RG (2007) Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization. Eur Heart J 28: 2018-2027
207. Klopsch C, Furlani D, Gabel R, Li W, Pittermann E, Ugurlucan M, Kundt G, Zingler C, Titze U, Wang W, Ong LL, Wagner K, Li RK, Ma N, Steinhoff G (2009) Intracardiac injection of erythropoietin induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model. J Cell Mol Med 13: 664-679
208. d'Uscio LV, Katusic ZS (2008) Erythropoietin increases endothelial biosynthesis of tetrahydrobiopterin by activation of protein kinase B alpha/Akt1. Hypertension 52: 93-99
209. Singh AK (2011) Is there a deleterious effect of erythropoietin in end-stage renal disease? Kidney Int 80: 569-571
210. Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, Feyzi JM, Ivanovich P, Kewalramani R, Levey AS, Lewis EF, McGill JB, McMurray JJ, Parfrey P, Parving HH, Remuzzi G, Singh AK, Solomon SD, Toto R (2009) A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 361: 2019-2032
211. Zhang Y, Thamer M, Kaufman JS, Cotter DJ, Hernan MA (2011) High doses of epoetin do not lower mortality and cardiovascular risk among elderly hemodialysis patients with diabetes. Kidney Int 80: 663-669
212. Weiner DE, Miskulin DC, Seefeld K, Ladik V, Zager PG, Singh AK, Johnson HK, Meyer KB (2007) Reducing versus discontinuing erythropoietin at high hemoglobin levels. J Am Soc Nephrol 18: 3184-3191
213. Corwin HL, Gettinger A, Fabian TC, May A, Pearl RG, Heard S, An R, Bowers PJ, Burton P, Klausner MA, Corwin MJ (2007) Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med 357: 965-976
214. Bohlius J, Wilson J, Seidenfeld J, Piper M, Schwarzer G, Sandercock J, Trelle S, Weingart O, Bayliss S, Brunskill S, Djulbegovic B, Benett CL, Langensiepen S, Hyde C, Engert E (2006) Erythropoietin or darbepoetin for patients with cancer. Cochrane Database Syst Rev. 3, CD003407
215. Tang YD, Rinder HM, Katz SD (2007) Effects of recombinant human erythropoietin on antiplatelet action of aspirin and clopidogrel in healthy subjects: results of a doubleblind, placebo-controlled randomized trial. Am Heart J 154(494):e491-e497
216. Stohlawetz PJ, Dzirlo L, Hergovich N, Lackner E, Mensik C, Eichler HG, Kabrna E, Geissler K, Jilma B (2000) Effects of erythropoietin on platelet reactivity and thrombopoiesis in humans. Blood 95: 2983-2989
217. Held TK, Gundert-Remy U (2010) Pharmacodynamic effects of haematopoietic cytokines: the view of a clinical oncologist. Basic Clin Pharmacol Toxicol 106: 210-214
218. Arcasoy MO (2008) Erythropoiesisstimulating agent use in cancer: preclinical and clinical perspectives. Clin Cancer Res 14: 4685-4690