Seminars in Fetal & Neonatal Medicine
Volume 15, Issue 4 , Pages 196-202 , August 2010

Hypoxia-inducible factor (HIF) and HIF-stabilizing agents in neonatal care

  • Angela M. Park

      Affiliations

    • Department of Pediatrics, University of California, San Francisco, CA, USA
    • ,
  • Timothy A. Sanders

      Affiliations

    • Department of Pediatrics, University of California, San Francisco, CA, USA
    • ,
  • Emin Maltepe

      Affiliations

    • Department of Pediatrics, University of California, San Francisco, CA, USA
    • Department of Biomedical Sciences, University of California, San Francisco, CA, USA
    • Center for Reproductive Sciences, University of California, San Francisco, CA, USA
    • Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, USA
    • Corresponding Author InformationCorresponding author. Departments of Pediatrics and Biomedical Sciences, Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, 513 Parnassus Ave. HSE-1424, San Francisco, CA 94143-1346, USA.

References 

  1. Maltepe E, Saugstad OD. Oxygen in health and disease: regulation of oxygen homeostasis – clinical implications. Pediatr Res. 2009;65:261–268
  2. Klimova T, Chandel NS. Mitochondrial complex III regulates hypoxic activation of HIF. Cell Death Differ. 2008;15:660–666
  3. Semenza GL. Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (Bethesda). 2009;24:97–106
  4. Dunwoodie SL. The role of hypoxia in development of the mammalian embryo. Dev Cell. 2009;17:755–773
  5. Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA. 1995;92:5510–5514
  6. Wang GL, Semenza GL. Purification and characterization of hypoxia-inducible factor 1. J Biol Chem. 1995;270:1230–1237
  7. Semenza GL, Nejfelt MK, Chi SM, Antonarakis SE. Hypoxia-inducible nuclear factors bind to an enhancer element located 3’ to the human erythropoietin gene. Proc Natl Acad Sci USA. 1991;88:5680–5684
  8. Semenza GL. Expression of hypoxia-inducible factor 1: mechanisms and consequences. Biochem Pharmacol. 2000;59:47–53
  9. Wenger RH, Stiehl DP, Camenisch G. Integration of oxygen signaling at the consensus HRE. Sci STKE. 2005;2005(306):re12
  10. Pugh CW, Ebert BL, Ebrahim O, Maxwell PH, Ratcliffe PJ. Analysis of cis-acting sequences required for operation of the erythropoietin 3’ enhancer in different cell lines. Ann NY Acad Sci. 1994;718:31–39discussion 9–40
  11. Bruick RK, McKnight SL. A conserved family of prolyl-4-hydroxylases that modify HIF. Science. 2001;294(5545):1337–1340
  12. Jaakkola P, Mole DR, Tian YM, et al. Targeting of HIF-alpha to the von Hippel–Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 2001;292(5516):468–472
  13. Ivan M, Kondo K, Yang H, et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science. 2001;292(5516):464–468
  14. Schofield CJ, Ratcliffe PJ. Signalling hypoxia by HIF hydroxylases. Biochem Biophys Res Commun. 2005;338:617–626
  15. Kim W, Kaelin WG. The von Hippel–Lindau tumor suppressor protein: new insights into oxygen sensing and cancer. Curr Opin Genet Dev. 2003;13:55–60
  16. Masson N, Willam C, Maxwell PH, Pugh CW, Ratcliffe PJ. Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation. EMBO J. 2001;20:5197–5206
  17. Lando D, Peet DJ, Gorman JJ, et al. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev. 2002;16:1466–1471
  18. Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML. Asparagine hydroxylation of the HIF transactivation domain – a hypoxic switch. Science. 2002;295(5556):858–861
  19. Kaelin WG, Ratcliffe PJ. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Molec Cell. 2008;30:393–402
  20. Kaelin WG. Proline hydroxylation and gene expression. Annu Rev Biochem. 2005;74:115–128
  21. Lieb ME, Menzies K, Moschella MC, Ni R, Taubman MB. Mammalian EGLN genes have distinct patterns of mRNA expression and regulation. Biochem Cell Biol. 2002;80:421–426
  22. Takeda K, Ho VC, Takeda H, et al. Placental but not heart defects are associated with elevated hypoxia-inducible factor α levels in mice lacking prolyl hydroxylase domain protein 2. Molec Cell Biol. 2006;26:8336–8346
  23. Minamishima YA, Moslehi J, Bardeesy N, et al. Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure. Blood. 2008;111:3236–3244
  24. Fong GH, Takeda K. Role and regulation of prolyl hydroxylase domain proteins. Cell Death Differ. 2008;15:635–641
  25. Jain S, Maltepe E, Lu MM, Simon C, Bradfield CA. Expression of ARNT, ARNT2, HIF1 alpha, HIF2 alpha and Ah receptor mRNAs in the developing mouse. Mech Dev. 1998;73:117–123
  26. Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC. Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Molec Cell Biol. 2003;23:9361–9374
  27. Skuli N, Liu L, Runge A, et al. Endothelial deletion of hypoxia-inducible factor-2alpha (HIF-2alpha) alters vascular function and tumor angiogenesis. Blood. 2009;114:469–477
  28. Covello KL, Kehler J, Yu H, et al. HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev. 2006;20:557–570
  29. Raval RR, Lau KW, Tran MG, et al. Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel–Lindau-associated renal cell carcinoma. Molec Cell Biol. 2005;25:5675–5686
  30. Gordan JD, Bertout JA, Hu CJ, Diehl JA, Simon MC. HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. Cancer Cell. 2007;11:335–347
  31. Makino Y, Cao R, Svensson K, et al. Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature. 2001;414(6863):550–554
  32. Chandel NS, Maltepe E, Goldwasser E, et al. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci USA. 1998;95:11715–11720
  33. Chandel NS, McClintock DS, Feliciano CE, et al. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem. 2000;275:25130–25138
  34. Brunelle JK, Bell EL, Quesada NM, et al. Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation. Cell Metab. 2005;1:409–414
  35. Guzy RD, Hoyos B, Robin E, et al. Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab. 2005;1:401–408
  36. Mansfield KD, Guzy RD, Pan Y, et al. Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab. 2005;1:393–399
  37. Gerald D, Berra E, Frapart YM, et al. JunD reduces tumor angiogenesis by protecting cells from oxidative stress. Cell. 2004;118:781–794
  38. Liu L, Simon MC. Regulation of transcription and translation by hypoxia. Cancer Biol Ther. 2004;3:492–497
  39. Salmeen A, Barford D. Functions and mechanisms of redox regulation of cysteine-based phosphatases. Antioxid Redox Signal. 2005;7:560–577
  40. Emerling BM, Platanias LC, Black E, et al. Mitochondrial reactive oxygen species activation of p38 mitogen-activated protein kinase is required for hypoxia signaling. Molec Cell Biol. 2005;25:4853–4862
  41. Okazaki K, Maltepe E. Oxygen, epigenetics and stem cell fate. Regen Med. 2006;1:71–83
  42. Goldwasser E. From protein to gene to protein: the molecular biology of erythropoietin. Am J Kidney Dis. 1991;18(4 Suppl. 1):10–13
  43. Yoon D, Pastore YD, Divoky V, et al. Hypoxia-inducible factor-1 deficiency results in dysregulated erythropoiesis signaling and iron homeostasis in mouse development. J Biol Chem. 2006;281:25703–25711
  44. Rolfs A, Kvietikova I, Gassmann M, Wenger RH. Oxygen-regulated transferrin expression is mediated by hypoxia-inducible factor-1. J Biol Chem. 1997;272:20055–20062
  45. Tacchini L, Bianchi L, Bernelli-Zazzera A, Cairo G. Transferrin receptor induction by hypoxia. HIF-1-mediated transcriptional activation and cell-specific post-transcriptional regulation. J Biol Chem. 1999;274:24142–24146
  46. Adelman DM, Maltepe E, Simon MC. Multilineage embryonic hematopoiesis requires hypoxic ARNT activity. Genes Dev. 1999;13:2478–2483
  47. Gruber M, Hu CJ, Johnson RS, et al. Acute postnatal ablation of Hif-2alpha results in anemia. Proc Natl Acad Sci USA. 2007;104:2301–2306
  48. Maltepe E, Schmidt JV, Baunoch D, Bradfield CA, Simon MC. Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT. Nature. 1997;386(6623):403–407
  49. Iyer NV, Kotch LE, Agani F, et al. Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev. 1998;12:149–162
  50. Kozak KR, Abbott B, Hankinson O. ARNT-deficient mice and placental differentiation. Dev Biol. 1997;191:297–305
  51. Ryan HE, Lo J, Johnson RS. HIF-1 alpha is required for solid tumor formation and embryonic vascularization. EMBO J. 1998;17:3005–3015
  52. Ozaki H, Yu AY, Della N, et al. Hypoxia inducible factor-1alpha is increased in ischemic retina: temporal and spatial correlation with VEGF expression. Invest Ophthalmol Vis Sci. 1999;40:182–189
  53. Gerber HP, Condorelli F, Park J, Ferrara N. Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes. Flt-1, but not Flk-1/KDR, is up-regulated by hypoxia. J Biol Chem. 1997;272:23659–23667
  54. Ding K, Scortegagna M, Seaman R, Birch DG, Garcia JA. Retinal disease in mice lacking hypoxia-inducible transcription factor-2alpha. Invest Ophthalmol Vis Sci. 2005;46:1010–1016
  55. Morita M, Ohneda O, Yamashita T, et al. HLF/HIF-2alpha is a key factor in retinopathy of prematurity in association with erythropoietin. EMBO J. 2003;22:1134–1146
  56. Chen C, Pore N, Behrooz A, Ismail-Beigi F, Maity A. Regulation of glut1 mRNA by hypoxia-inducible factor-1. Interaction between H-ras and hypoxia. J Biol Chem. 2001;276:9519–9525
  57. Gunton JE, Kulkarni RN, Yim S, et al. Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes. Cell. 2005;122:337–349
  58. Wang XL, Suzuki R, Lee K, et al. Ablation of ARNT/HIF1beta in liver alters gluconeogenesis, lipogenic gene expression, and serum ketones. Cell Metab. 2009;9:428–439
  59. Hung MS, Avner P, Rogner UC. Identification of the transcription factor ARNTL2 as a candidate gene for the type 1 diabetes locus Idd6. Hum Mol Genet. 2006;15:2732–2742
  60. Woon PY, Kaisaki PJ, Braganca J, et al. Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes. Proc Natl Acad Sci USA. 2007;104:14412–14417
  61. Das SK, Sharma NK, Chu WS, Wang H, Elbein SC. Aryl hydrocarbon receptor nuclear translocator (ARNT) gene as a positional and functional candidate for type 2 diabetes and prediabetic intermediate traits: mutation detection, case–control studies, and gene expression analysis. BMC Med Genet. 2008;9:16
  62. Eichenwald EC, Stark AR. Management and outcomes of very low birth weight. N Engl J Med. 2008;358:1700–1711
  63. Carpenter T, Schomberg S, Steudel W, et al. Endothelin B receptor deficiency predisposes to pulmonary edema formation via increased lung vascular endothelial cell growth factor expression. Circ Res. 2003;93:456–463
  64. Asikainen TM, Ahmad A, Schneider BK, White CW. Effect of preterm birth on hypoxia-inducible factors and vascular endothelial growth factor in primate lungs. Pediatr Pulmonol. 2005;40:538–546
  65. Compernolle V, Brusselmans K, Acker T, et al. Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med. 2002;8:702–710
  66. Le Cras TD, Markham NE, Tuder RM, Voelkel NF, Abman SH. Treatment of newborn rats with a VEGF receptor inhibitor causes pulmonary hypertension and abnormal lung structure. Am J Physiol Lung Cell Mol Physiol. 2002;283:L555–L562
  67. Henry MC, Moss RL. Necrotizing enterocolitis. Annu Rev Med. 2009;60:111–124
  68. Karhausen J, Furuta GT, Tomaszewski JE, et al. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J Clin Invest. 2004;114:1098–1106
  69. Louis NA, Hamilton KE, Canny G, et al. Selective induction of mucin-3 by hypoxia in intestinal epithelia. J Cell Biochem. 2006;99:1616–1627
  70. Hernandez C, Santamatilde E, McCreath KJ, et al. Induction of trefoil factor (TFF)1, TFF2 and TFF3 by hypoxia is mediated by hypoxia inducible factor-1: implications for gastric mucosal healing. Br J Pharmacol. 2009;156:262–272
  71. Nizet V, Johnson RS. Interdependence of hypoxic and innate immune responses. Nat Rev Immunol. 2009;9:609–617
  72. Rius J, Guma M, Schachtrup C, et al. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature. 2008;453(7196):807–811
  73. Sears JE, Hoppe G, Ebrahem Q, Anand-Apte B. Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy. Proc Natl Acad Sci USA. 2008;105:19898–19903
  74. Asikainen TM, Chang LY, Coalson JJ, et al. Improved lung growth and function through hypoxia-inducible factor in primate chronic lung disease of prematurity. FASEB J. 2006;20:1698–1700
  75. Asikainen TM, Waleh NS, Schneider BK, Clyman RI, White CW. Enhancement of angiogenic effectors through hypoxia-inducible factor in preterm primate lung in vivo. Am J Physiol Lung Cell Mol Physiol. 2006;291:L588–L595

PII: S1744-165X(10)00042-9

doi: 10.1016/j.siny.2010.05.006

Seminars in Fetal & Neonatal Medicine
Volume 15, Issue 4 , Pages 196-202 , August 2010

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