Isocitrate ameliorates anemia by suppressing the erythroid iron restriction response

Journal of Clinical Investigation

Volumn 123, Issue 8, 2013, Pages 3614-3623

  Richardson, Chanté L ^a   Delehanty, Lorrie L ^a   Bullock, Grant C ^a,c   Rival, Claudia M ^a   Tung, Kenneth S ^a   Kimpel, Donald L ^a   Gardenghi, Sara ^b   Rivella, Stefano ^b   Goldfarb, Adam N ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

^c UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ISOCITRIC ACID; TRANSCRIPTION FACTOR PU 1;

ANEMIA; ANEMIA OF CHRONIC DISEASE AND INFLAMMATION; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; ERYTHROID PRECURSOR CELL; ERYTHROPOIESIS; FEMALE; IN VITRO STUDY; IRON RESTRICTION; NONHUMAN; PRIORITY JOURNAL; RAT; UPREGULATION;

ACONITATE HYDRATASE; ANEMIA; ANIMALS; CELLS, CULTURED; ERYTHROID CELLS; ERYTHROPOIESIS; FEMALE; HUMANS; INTERFERON-GAMMA; IRON; ISOCITRATES; PROTEIN KINASE C; PROTO-ONCOGENE PROTEINS; RATS; RATS, INBRED LEW; SIGNAL TRANSDUCTION; TRANS-ACTIVATORS; TRANSCRIPTIONAL ACTIVATION;

EID: 84881239640     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI68487     Document Type: Article

References (60)

1. Goodnough LT, Nemeth E, Ganz T. Detection, evaluation, and management of iron-restricted erythropoiesis. Blood. 2010;116(23):4754-4761.
2. Spivak JL, Gascón P, Ludwig H. Anemia management in oncology and hematology. Oncologist. 2009; 14(suppl 1):43-56.
3. McClellan WM, Jurkovitz C, Abramson J. The epidemiology and control of anaemia among pre- ESRD patients with chronic kidney disease. Eur J Clin Invest. 2005;35(suppl 3):58-65.
4. Brookhart MA, Schneeweiss S, Avorn J, Bradbury BD, Liu J, Winkelmayer WC. Comparative mortality risk of anemia management practices in incident hemodialysis patients. JAMA. 2010;303(9):857-864.
5. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011-1023.
6. Ganz T. Hepcidin and iron regulation, 10 years later. Blood. 2011;117(17):4425-4433.
7. Weiss G. Pathogenesis and treatment of anaemia of chronic disease. Blood Rev. 2002;16(2):87-96.
8. Theurl I, Mattle V, Seifert M, Mariani M, Marth C, Weiss G. Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease. Blood. 2006; 107(10):4142-4148.
9. Tussing-Humphreys L, Pusatcioglu C, Nemeth E, Braunschweig C. Rethinking iron regulation and assessment in iron deficiency, anemia of chronic disease, and obesity: introducing hepcidin. J Acad Nutr Diet. 2012;112(3):391-400.
10. Sun CC, Vaja V, Babitt JL, Lin HY. Targeting the hepcidin-ferroportin axis to develop new treatment strategies for anemia of chronic disease and anemia of inflammation. Am J Hematol. 2012;87(4):392-400.
11. Coulon S, et al. Polymeric IgA1 controls erythroblast proliferation and accelerates erythropoiesis recovery in anemia. Nat Med. 2011;17(11):1456-1465.
12. Bullock GC, et al. Iron control of erythroid development by a novel aconitase-associated regulatory pathway. Blood. 2010;116(1):97-108.
13. Talbot AL, Bullock GC, Delehanty LL, Sattler M, Zhao ZJ, Goldfarb AN. Aconitase regulation of erythropoiesis correlates with a novel licensing function in erythropoietin-induced ERK signaling. PLoS One. 2011;6(8):e23850.
14. Geerts I, Vermeersch P, Joosten E. Evaluation of the first commercial hepcidin ELISA for the differential diagnosis of anemia of chronic disease and iron deficiency anemia in hospitalized geriatric patients. ISRN Hematol. 2012;2012:567491.
15. Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC. Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood. 2002;100(10):3776-3781.
16. Finberg KE, et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet. 2008;40(5):569-571.
17. Prince OD, et al. Late stage erythroid precursor production is impaired in mice with chronic inflammation. Haematologica. 2012;97(11):1648-1656.
18. Weiss G, Gordeuk VR. Benefits and risks of iron therapy for chronic anaemias. Eur J Clin Invest. 2005; 35(suppl 3):36-45.
19. Sengölge G, Hörl WH, Sunder-Plassmann G. Intravenous iron therapy: well-tolerated, yet not harmless. Eur J Clin Invest. 2005;35(suppl 3):46-51.
20. Theurl I, et al. Pathways for the regulation of hepcidin expression in anemia of chronic disease and iron deficiency anemia in vivo. Haematologica. 2011; 96(12):1761-1769.
21. Pop R, et al. A key commitment step in erythropoiesis is synchronized with the cell cycle clock through mutual inhibition between PU.1 and S-phase progression. PLoS Biol. 2010;8(9):e1000484.
22. Libregts SF, et al. Chronic IFN-γ production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF-1/PU.1 axis. Blood. 2011;118(9):2578-2588.
23. Coccia MA, et al. Novel erythropoiesis stimulating protein (darbepoetin alfa) alleviates anemia associated with chronic inflammatory disease in a rodent model. Exp Hematol. 2001;29(10):1201-1209.
24. Theurl I, et al. Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications. Blood. 2009;113(21):5277-5286.
25. Sartor RB, Anderle SK, Rifai N, Goo DA, Cromartie WJ, Schwab JH. Protracted anemia associated with chronic, relapsing systemic inflammation induced by arthropathic peptidoglycan-polysaccharide polymers in rats. Infect Immun. 1989;57(4):1177-1185.
26. Ganz T, Nemeth E. Iron metabolism: interactions with normal and disordered erythropoiesis. Cold Spring Harb Perspect Med. 2012;2(5):a011668.
27. Thawani N, Tam M, Chang K, Stevenson MM. Interferon- gamma mediates suppression of erythropoiesis but not reduced red cell survival following CpGODN administration in vivo. Exp Hematol. 2006; 34(11):1451-1461.
28. Allen DA, Breen C, Yaqoob MM, Macdougall IC. Inhibition of CFU-E colony formation in uremic patients with inflammatory disease: role of IFN-gamma and TNF-alpha. J Investig Med. 1999; 47(5):204-211.
29. Means RT Jr, Dessypris EN, Krantz SB. Inhibition of human erythroid colony-forming units by interleukin- 1 is mediated by gamma interferon. J Cell Physiol. 1992;150(1):59-64.
30. Means RT Jr, Krantz SB. Inhibition of human erythroid colony-forming units by tumor necrosis factor requires beta interferon. J Clin Invest. 1993; 91(2):416-419.
31. Canal F, Fosset C, Chauveau MJ, Drapier JC, Bouton C. Regulation of the cysteine desulfurase Nfs1 and the scaffold protein IscU in macrophages stimulated with interferon-gamma and lipopolysaccharide. Arch Biochem Biophys. 2007;465(1):282-292.
32. Halupa A, Bailey ML, Huang K, Iscove NN, Levy DE, Barber DL. A novel role for STAT1 in regulating murine erythropoiesis: deletion of STAT1 results in overall reduction of erythroid progenitors and alters their distribution. Blood. 2005; 105(2):552-561.
33. Oexle H, et al. Pathways for the regulation of interferon- gamma-inducible genes by iron in human monocytic cells. J Leukoc Biol. 2003;74(2):287-294.
34. Regis G, et al. Iron regulates T-lymphocyte sensitivity to the IFN-gamma/STAT1 signaling pathway in vitro and in vivo. Blood. 2005;105(8):3214-3221.
35. Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon- gamma: an overview of signals, mechanisms and functions. J Leukoc Biol. 2004;75(2):163-189.
36. Wontakal SN, et al. A core erythroid transcriptional network is repressed by a master regulator of myelo-lymphoid differentiation. Proc Natl Acad Sci U S A. 2012;109(10):3832-3837.
37. Ravet E, et al. Characterization of DNA-binding- dependent and -independent functions of SCL/TAL1 during human erythropoiesis. Blood. 2004;103(9):3326-3335.
38. Freyssinier JM, et al. Purification, amplification and characterization of a population of human erythroid progenitors. Br J Haematol. 1999;106(4):912-922.
39. Back J, Dierich A, Bronn C, Kastner P, Chan S. PU.1 determines the self-renewal capacity of erythroid progenitor cells. Blood. 2004;103(10):3615- 3623.
40. Mazzi P, Donini M, Margotto D, Wientjes F, Dusi S. IFN-gamma induces gp91phox expression in human monocytes via protein kinase C-dependent phosphorylation of PU.1. J Immunol. 2004; 172(8):4941-4947.
41. Xue Y, Alford P, Shackelford RE. Protein kinase C activation increases binding of transcription factor PU.1 in murine tissue macrophages. Biochem Biophys Res Commun. 1999;254(1):211-214.
42. Van Buren P, Velez RL, Vaziri ND, Zhou XJ. Iron overdose: a contributor to adverse outcomes in randomized trials of anemia correction in CKD. Int Urol Nephrol. 2012;44(2):499-507.
43. Rostoker G, et al. Hemodialysis-associated hemosiderosis in the era of erythropoiesis-stimulating agents: a MRI study. Am J Med. 2012;125(10):991-999. e1.
44. Sasu BJ, et al. Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia. Blood. 2010;115(17):3616-3624.
45. Theurl I, et al. Pharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats. Blood. 2011;118(18):4977-4984.
46. Kurz K, Gluhcheva Y, Zvetkova E, Konwalinka G, Fuchs D. Interferon-gamma-mediated pathways are induced in human CD34(+) haematopoietic stem cells. Immunobiology. 2010;215(6):452-457.
47. Leddin M, et al. Two distinct auto-regulatory loops operate at the PU.1 locus in B cells and myeloid cells. Blood. 2011;117(10):2827-2838.
48. McIvor Z, et al. Transient expression of PU.1 commits multipotent progenitors to a myeloid fate whereas continued expression favors macrophage over granulocyte differentiation. Exp Hematol. 2003; 31(1):39-47.
49. Nerlov C, Graf T. PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors. Genes Dev. 1998;12(15):2403-2412.
50. Oduro KA Jr, et al. Myeloid skewing in murine autoimmune arthritis occurs in hematopoietic stem and primitive progenitor cells. Blood. 2012; 120(11):2203-2213.
51. Goldfarb AN, Wong D, Racke FK. Induction of megakaryocytic differentiation in primary human erythroblasts: a physiological basis for leukemic lineage plasticity. Am J Pathol. 2001;158(4):1191-1198.
52. DeKoter RP, Singh H. Regulation of B lymphocyte and macrophage development by graded expression of PU.1. Science. 2000;288(5470):1439-1441.
53. Nobes PR, Carter AB. Reticulocyte counting using flow cytometry. J Clin Pathol. 1990;43(8):675-678.
54. Choi Y, Elagib KE, Delehanty LL, Goldfarb AN. Erythroid inhibition by the leukemic fusion AML1- ETO is associated with impaired acetylation of the major erythroid transcription factor GATA-1. Cancer Res. 2006;66(6):2990-2996.
55. Kakiuchi S, Ohara S, Ogata S, Miura D, Kasahara Y, Izawa Y. Flow cytometric analyses on lineagespecific cell surface antigens of rat bone marrow to seek potential myelotoxic biomarkers: status after repeated dose of 5-fluorouracil. J Toxicol Sci. 2004; 29(2):101-111.
56. Koulnis M, et al. Contrasting dynamic responses in vivo of the Bcl-xL and Bim erythropoietic survival pathways. Blood. 2012;119(5):1228-1239.
57. Tong W, Rouault TA. Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis. Cell Metab. 2006;3(3):199-210.
58. ABI PRISM 7700 Sequence Detection System. User bulletin #2. Applied Biosystems. December 11, 1997. Updated October 2001.
59. Elagib KE, et al. Cross-talk of GATA-1 and P-TEFb in megakaryocyte differentiation. Blood. 2008; 112(13):4884-4894.
60. Rubinstein JD, Elagib KE, Goldfarb AN. Cyclic AMP signaling inhibits megakaryocytic differentiation by targeting transcription factor 3 (E2A) cyclin-dependent kinase inhibitor 1A (CDKN1A) transcriptional axis. J Biol Chem. 2012; 287(23):19207-19215. Diseases Diseases