2-Oxoglutarate-dependent oxygenases control hepcidin gene expression

Journal of Hepatology

Volumn 48, Issue 5, 2008, Pages 801-810

  Braliou, Georgia G ^a   Verga Falzacappa, Maria Vittoria ^b,c   Chachami, Georgia ^a,d   Casanovas, Guillem ^b,c   Muckenthaler, Martina U ^b,c   Simos, George ^a,d  

^a UNIVERSITY OF THESSALY   (Greece)

^b UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^c Molecular Medicine Partnership Unit   (Germany)

^d INSTITUTE OF HUMAN PERFORMANCE AND REHABILITATION   (Greece)

Author keywords

2 Oxoglutarate dependent oxygenases; Cobalt; DFO; DMOG; Hepcidin; HIF 1; Hypoxia; IL 6; Protein hydroxylation

Indexed keywords

2 OXOGLUTARATE DEPENDENT OXYGENASE; 2 OXOGLUTARIC ACID; BONE MORPHOGENETIC PROTEIN; COBALT; DEFEROXAMINE; DIMETHYLOXALYLGLYCINE; HEPCIDIN; HYPOXIA INDUCIBLE FACTOR 1; INTERLEUKIN 6; MESSENGER RNA; OXYGENASE; REACTIVE OXYGEN METABOLITE; STAT PROTEIN; TRANSCRIPTION FACTOR AP 1; UNCLASSIFIED DRUG;

ARTICLE; CELL CULTURE; CELL HYPOXIA; CONTROLLED STUDY; DOWN REGULATION; ENZYME ACTIVITY; ENZYME INHIBITION; GENE CONTROL; GENE EXPRESSION; GENE REPRESSION; GENETIC TRANSFECTION; HEPATOMA CELL; HUMAN; HUMAN CELL; NORTHERN BLOTTING; PRIORITY JOURNAL; PROMOTER REGION; REAL TIME POLYMERASE CHAIN REACTION;

ANTIMICROBIAL CATIONIC PEPTIDES; CELL LINE, TUMOR; GENE EXPRESSION REGULATION; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1; INTERLEUKIN-6; KETOGLUTARIC ACIDS; OXYGENASES; PROMOTER REGIONS (GENETICS); REACTIVE OXYGEN SPECIES; STAT TRANSCRIPTION FACTORS; TRANSCRIPTION FACTOR AP-1;

EID: 40949120506     PISSN: 01688278     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jhep.2007.12.021     Document Type: Article

References (54)

1. Nemeth E., and Ganz T. Regulation of iron metabolism by hepcidin. Annu Rev Nutr 26 (2006) 323-342
2. Nemeth E., Tuttle M.S., Powelson J., Vaughn M.B., Donovan A., Ward D.M., et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306 (2004) 2090-2093
3. Hentze M.W., Muckenthaler M.U., and Andrews N.C. Balancing acts: molecular control of mammalian iron metabolism. Cell 117 (2004) 285-297
4. Pietrangelo A., and Trautwein C. Mechanisms of disease: the role of hepcidin in iron homeostasis - implications for hemochromatosis and other disorders. Nat Clin Pract Gastroenterol Hepatol 1 (2004) 39-45
5. Papanikolaou G., and Pantopoulos K. Iron metabolism and toxicity. Toxicol Appl Pharmacol 202 (2005) 199-211
6. Nemeth E., and Ganz T. Hepcidin and iron-loading anemias. Haematologica 91 (2006) 727-732
7. Pietrangelo A., Dierssen U., Valli L., Garuti C., Rump A., Corradini E., et al. STAT3 is required for IL-6-gp130-dependent activation of hepcidin in vivo. Gastroenterology 132 (2007) 294-300
8. Verga Falzacappa M.V., Vujic Spasic M., Kessler R., Stolte J., Hentze M.W., and Muckenthaler M.U. STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation. Blood 109 (2007) 353-358
9. Wrighting D.M., and Andrews N.C. Interleukin-6 induces hepcidin expression through STAT3. Blood 108 (2006) 3204-3209
10. Camaschella C. Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood 106 (2005) 3710-3717
11. Pietrangelo A. Hereditary hemochromatosis. Annu Rev Nutr 26 (2006) 251-270
12. Wang R.H., Li C., Xu X., Zheng Y., Xiao C., Zerfas P., et al. A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression. Cell Metab 2 (2005) 399-409
13. Babitt J.L., Huang F.W., Wrighting D.M., Xia Y., Sidis Y., Samad T.A., et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet 38 (2006) 531-539
14. Truksa J., Peng H., Lee P., and Beutler E. Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Proc Natl Acad Sci USA 103 (2006) 10289-10293
15. Pak M., Lopez M.A., Gabayan V., Ganz T., and Rivera S. Suppression of hepcidin during anemia requires erythropoietic activity. Blood 108 (2006) 3730-3735
16. Vokurka M., Krijt J., Sulc K., and Necas E. Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis. Physiol Res 55 (2006) 667-674
17. Nicolas G., Chauvet C., Viatte L., Danan J.L., Bigard X., Devaux I., et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 110 (2002) 1037-1044
18. Kaelin W.G. Proline hydroxylation and gene expression. Annu Rev Biochem 74 (2005) 115-128
19. Schofield C.J., and Ratcliffe P.J. Signalling hypoxia by HIF hydroxylases. Biochem Biophys Res Commun 338 (2005) 617-626
20. Hirota K., and Semenza G.L. Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases. Biochem Biophys Res Commun 338 (2005) 610-616
21. Fandrey J., Gorr T.A., and Gassmann M. Regulating cellular oxygen sensing by hydroxylation. Cardiovasc Res 71 (2006) 642-651
22. Kietzmann T., and Gorlach A. Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression. Semin Cell Dev Biol 16 (2005) 474-486
23. Simon M.C. Siah proteins, HIF prolyl hydroxylases, and the physiological response to hypoxia. Cell 117 (2004) 851-853
24. Hirsila M., Koivunen P., Xu L., Seeley T., Kivirikko K.I., and Myllyharju J. Effect of desferrioxamine and metals on the hydroxylases in the oxygen sensing pathway. FASEB J 19 (2005) 1308-1310
25. Epstein A.C., Gleadle J.M., McNeill L.A., Hewitson K.S., O'Rourke J., Mole D.R., et al. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107 (2001) 43-54
26. 2-regulated prolyl hydroxylation. Science 292 (2001) 468-472
27. Berchner-Pfannschmidt U., Yamac H., Trinidad B., and Fandrey J. Nitric oxide modulates oxygen sensing by hypoxia-inducible factor 1-dependent induction of prolyl hydroxylase 2. J Biol Chem 282 (2007) 1788-1796
28. Vissers M.C., Gunningham S.P., Morrison M.J., Dachs G.U., and Currie M.J. Modulation of hypoxia-inducible factor-1 alpha in cultured primary cells by intracellular ascorbate. Free Radic Biol Med 42 (2007) 765-772
29. Lu H., Dalgard C.L., Mohyeldin A., McFate T., Tait A.S., and Verma A. Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1. J Biol Chem 280 (2005) 41928-41939
30. Pan Y., Mansfield K.D., Bertozzi C.C., Rudenko V., Chan D.A., Giaccia A.J., et al. Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Mol Cell Biol 27 (2007) 912-925
31. Courselaud B., Pigeon C., Inoue Y., Inoue J., Gonzalez F.J., Leroyer P., et al. C/EBPalpha regulates hepatic transcription of hepcidin, an antimicrobial peptide and regulator of iron metabolism. Cross-talk between C/EBP pathway and iron metabolism. J Biol Chem 277 (2002) 41163-41170
32. Verga Falzacappa MV, Casanovas G, Hentze MW, Muckenthaler MU. A Bone Morphogenetic Protein (BMP) responsive element in the hepcidin promoter controls HFE2-mediated hepatic hepcidin expression and its response to IL-6 in cultured cells. J Molec Med; in press.
33. Shibata T., Giaccia A.J., and Brown J.M. Development of a hypoxia-responsive vector for tumor-specific gene therapy. Gene Ther 7 (2000) 493-498
34. Chachami G., Simos G., Hatziefthimiou A., Bonanou S., Molyvdas P.A., and Paraskeva E. Cobalt induces hypoxia-inducible factor-1alpha expression in airway smooth muscle cells by a reactive oxygen species- and PI3K-dependent mechanism. Am J Respir Cell Mol Biol 31 (2004) 544-551
35. Mylonis I., Chachami G., Samiotaki M., Panayotou G., Paraskeva E., Kalousi A., et al. Identification of MAPK phosphorylation sites and their role in the localization and activity of hypoxia-inducible factor 1α. J Biol Chem 281 (2006) 33095-33106
36. Church G.M., and Gilbert W. Genomic sequencing. Proc Natl Acad Sci USA 81 (1984) 1991-1995
37. Andriopoulos B., and Pantopoulos K. Hepcidin generated by hepatoma cells inhibits iron export from co-cultured THP1 monocytes. J Hepatol 44 (2006) 1125-1131
38. Pore N., Liu S., Shu H.K., Li B., Haas-Kogan D., Stokoe D., et al. Sp1 is involved in Akt-mediated induction of VEGF expression through an HIF-1-independent mechanism. Mol Biol Cell 15 (2004) 4841-4853
39. Denissov S., van Driel M., Voit R., Hekkelman M., Hulsen T., Hernandez N., et al. Identification of novel functional TBP-binding sites and general factor repertoires. EMBO J 26 (2007) 944-954
40. Lyberopoulou A., Venieris E., Mylonis I., Chachami G., Pappas I., Simos G., et al. MgcRacGAP interacts with HIF-1α and regulates its transcriptional activity. Cell Physiol Biochem 20 (2007) 95-1006
41. Gray M.J., Zhang J., Ellis L.M., Semenza G.L., Evans D.B., Watowich S.S., et al. HIF-1alpha, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas. Oncogene 24 (2005) 3110-3120
42. Bayele H.K., McArdle H., and Srai S.K. Cis and trans regulation of hepcidin expression by upstream stimulatory factor. Blood 108 (2006) 4237-4245
43. 2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol 15 (1999) 551-578
44. Mazure N.M., Chauvet C., Bois-Joyeux B., Bernard M.A., Nacer-Cherif H., and Danan J.L. Repression of alpha-fetoprotein gene expression under hypoxic conditions in human hepatoma cells: characterization of a negative hypoxia response element that mediates opposite effects of hypoxia inducible factor-1 and c-Myc. Cancer Res 62 (2002) 1158-1165
45. Choi S.O., Cho Y.S., Kim H.L., and Park J.W. ROS mediate the hypoxic repression of the hepcidin gene by inhibiting C/EBPalpha and STAT-3. Biochem Biophys Res Commun 356 (2007) 312-317
46. Triantafyllou A., Liakos P., Tsakalof A., Georgatsou E., Simos G., and Bonanou S. Cobalt induces hypoxia-inducible factor-1alpha (HIF-1alpha) in HeLa cells by an iron-independent, but ROS-, PI-3K- and MAPK-dependent mechanism. Free Radic Res 40 (2006) 847-856
47. Harrison-Findik D.D., Schafer D., Klein E., Timchenko N.A., Kulaksiz H., Clemens D., et al. Alcohol metabolism-mediated oxidative stress down-regulates hepcidin transcription and leads to increased duodenal iron transporter expression. J Biol Chem 281 (2006) 22974-22982
48. Kuznetsova A.V., Meller J., Schnell P.O., Nash J.A., Ignacak M.L., Sanchez Y., et al. von Hippel-Lindau protein binds hyperphosphorylated large subunit of RNA polymerase II through a proline hydroxylation motif and targets it for ubiquitination. Proc Natl Acad Sci USA 100 (2003) 2706-2711
49. Hanson E.S., Rawlins M.L., and Leibold E.A. Oxygen and iron regulation of iron regulatory protein 2. J Biol Chem 278 (2003) 40337-40342
50. Wang J., Chen G., Muckenthaler M., Galy B., Hentze M.W., and Pantopoulos K. Iron-mediated degradation of IRP2, an unexpected pathway involving a 2-oxoglutarate-dependent oxygenase activity. Mol Cell Biol 24 (2004) 954-965
51. Cummins E.P., Berra E., Comerford K.M., Ginouves A., Fitzgerald K.T., Seeballuck F., et al. Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity. Proc Natl Acad Sci USA 103 (2006) 18154-18159
52. Cockman M.E., Lancaster D.E., Stolze I.P., Hewitson K.S., McDonough M.A., Coleman M.L., et al. Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH). Proc Natl Acad Sci USA 103 (2006) 14767-14772
53. Hagen T., Taylor C.T., Lam F., and Moncada S. Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1alpha. Science 302 (2003) 1975-1978
54. Stiehl D.P., Wirthner R., Koditz J., Spielmann P., Camenisch G., and Wenger R.H. Increased prolyl 4-hydroxylase domain proteins compensate for decreased oxygen levels. Evidence for an autoregulatory oxygen-sensing system. J Biol Chem 281 (2006) 23482-23491