Seminars in Nephrology
Volume 26, Issue 6 , Pages 454-465 , November 2006

Interrelationships Among Hypoxia-Inducible Factor Biology and Acid-Base Equilibrium

  • Henry N. Hulter

      Affiliations

    • Dr. Henry N. Hulter has been a consultant to Fibrogen, Inc. and Genentech, Inc.
    • ,
  • Reto Krapf

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Reto Krapf, MD, Department of Internal Medicine, University of Basel, Kantonsspital, C_4101 Bruderholz, Switzerland.

References 

  1. Maxwell PH, Wiesener MS, Chang GW, et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature. 1999;399:271–275
  2. Iyer NV, Leung SW, Semenza GL. The human hypoxia-inducible factor 1alpha gene: HIF1A structure and evolutionary conservation. Genomics. 1998;52:159–165
  3. Wang GL, Jiang BH, Rue EA, et al. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995;92:5510–5514
  4. D’Angelo G, Duplan E, Boyer N, et al. Hypoxia up-regulates prolyl hydroxylase activity: A feedback mechanism that limits HIF-1 responses during reoxygenation. J Biol Chem. 2003;278:38183–38187
  5. Huang LE, Pete EA, Schau M, et al. Leu-574 of HIF-1alpha is essential for the von Hippel-Lindau (VHL)-mediated degradation pathway. J Biol Chem. 2002;277:41750–41755
  6. Gray MJ, Zhang J, Ellis LM, 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. 2005;24:3110–3120
  7. Kallio PJ, Pongratz I, Gradin K, et al. Activation of hypoxia-inducible factor 1alpha: Posttranscriptional regulation and conformational change by recruitment of the Arnt transcription factor. Proc Natl Acad Sci U S A. 1997;94:5667–5672
  8. Bing OH, Brooks WW, Messer JV. Heart muscle viability following hypoxia: Protective effect of acidosis. Science. 1973;180:1297–1298
  9. Penttila A, Trump BF. Extracellular acidosis protects Ehrlich ascites tumor cells and rat renal cortex against anoxic injury. Science. 1974;185:277–278
  10. Kaku DA, Giffard RG, Choi DW. Neuroprotective effects of glutamate antagonists and extracellular acidity. Science. 1993;260:1516–1518
  11. Currin RT, Gores GJ, Thurman RG, et al. Protection by acidotic pH against anoxic cell killing in perfused rat liver: Evidence for a pH paradox. FASEB J. 1991;5:207–210
  12. Willam C, Warnecke C, Schefold JC, et al. Inconsistent effects of acidosis on HIF-alpha protein and its target genes. Pflugers Arch. 2006;451:534–543
  13. Christou H, Bailey N, Kluger MS, et al. Extracellular acidosis induces heme oxygenase-1 expression in vascular smooth muscle cells. Am J Physiol. 2005;288:H2647–H2652
  14. Mekhail K, Gunaratnam L, Bonicalzi ME, et al. HIF activation by pH-dependent nucleolar sequestration of VHL. Nat Cell Biol. 2004;6:642–647
  15. Mekhail K, Khacho M, Carrigan A, et al. Regulation of ubiquitin ligase dynamics by the nucleolus. J Cell Biol. 2005;170(5):733–744Aug 29.
  16. Amirand C, Mentre P, van de Geijn S, Waksmundzka M, Debey P. Intracellular pH in one-cell mouse embryo differs between subcellular compartments and between interphase and mitosis. Biol Cell. 2000;92(6):409–419Sep
  17. Mekhail K, Khacho M, Gunaratnam L, Lee S. Oxygen sensing by H+: implications for HIF and hypoxic cell memory. Cell Cycle. 2004;3:1027–1029
  18. Seagroves TN, Ryan HE, Lu H, et al. Transcription factor HIF-1 is a necessary mediator of the Pasteur effect in mammalian cells. Mol Cell Biol. 2001;21:3436–3444
  19. Luo F, Liu X, Yan N, et al. Hypoxia-inducible transcription factor-1alpha promotes hypoxia-induced A549 apoptosis via a mechanism that involves the glycolysis pathway. BMC Cancer. 2006;6:26
  20. Savai R, Schermuly RT, Voswinckel R, et al. HIF-1alpha attenuates tumor growth in spite of augmented vascularization in an A549 adenocarcinoma mouse model. Int J Oncol. 2005;27:393–400
  21. Acker T, Diez-Juan A, Aragones J, et al. Genetic evidence for a tumor suppressor role of HIF-2alpha. Cancer Cell. 2005;8:131–141
  22. Kim JW, Tchernyshyov I, Semenza GL, et al. HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3:177–185
  23. Lim JH, Park JW, Kim MS, et al. Bafilomycin induces the p21-mediated growth inhibition of cancer cells under hypoxic conditions by expressing HIF-1α. Mol Pharmacol. 2006;70:1856–1865
  24. Semenza GL. Baffled by Bafilomycin: An anti-cancer agent that induces HIF-1α expression. Mol Pharmacol. 2006;70:1841–1843
  25. Sennoune SR, Bakunts K, Martinez GM, et al. Vacuolar H+-ATPase in human breast cancer cells with distinct metastatic potential: Distribution and functional activity. Am J Physiol. 2004;286:C1443–C1452
  26. Martinez-Zaguilan R, Lynch RM, Martinez GM, et al. Vacuolar-type H(+)-ATPases are functionally expressed in plasma membranes of human tumor cells. Am J Physiol. 1993;265:C1015–C1029
  27. Martinez-Zaguilan R, Martinez GM, Gomez A, et al. Distinct regulation of pHi and [Ca2+]i in human melanoma cells with different metastatic potential. J Cell Physiol. 1998;176:196–205
  28. Ihnatko R, Kubes M, Takacova M, et al. Extracellular acidosis elevates carbonic anhydrase IX in human glioblastoma cells via transcriptional modulation that does not depend on hypoxia. Int J Oncol. 2006;29:1025–1033
  29. Lu H, Forbes RA, Verma A. Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem. 2002;277:23111–23115
  30. Shuin T, Yamasaki I, Tamura K, et al. Von Hippel-Lindau disease: Molecular pathological basis, clinical criteria, genetic testing, clinical features of tumors and treatment. Jpn J Clin Oncol. 2006;36:337–343
  31. Pastore Y, Jedlickova K, Guan Y, et al. Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia [erratum in: Am J Hum Genet 74:598, 2004]. Am J Hum Genet. 2003;73:412–419
  32. Bento MC, Chang KT, Guan Y, et al. Congenital polycythemia with homozygous and heterozygous mutations of von Hippel-Lindau gene: Five new Caucasian patients. Haematologica. 2005;90:128–129
  33. Ang SO, Chen H, Hirota K, et al. Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. Nat Genet. 2002;32:614–621
  34. Rathmell WK, Hickey MM, Bezman NA, et al. In vitro and in vivo models analyzing von Hippel-Lindau disease-specific mutations. Cancer Res. 2004;64:8595–8603
  35. Hoffman MA, Ohh M, Yang H, et al. von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the ability to downregulate HIF. Hum Mol Genet. 2001;10:1019–1027
  36. Maranchie JK, Vasselli JR, Riss J, et al. The contribution of VHL substrate binding and HIF1-alpha to the phenotype of VHL loss in renal cell carcinoma. Cancer Cell. 2002;1:247–255
  37. Roe JS, Youn HD. The positive regulation of p53 by the tumor suppressor VHL. Cell Cycle. 2006;15:5;[E-pub ahead of print]
  38. Okuda H, Saitoh K, Hirai S, et al. The von Hippel-Lindau tumor suppressor protein mediates ubiquitination of activated atypical protein kinase C. J Biol Chem. 2001;276:43611–43617
  39. Datta K, Nambudripad R, Pal S, et al. Inhibition of insulin-like growth factor-I-mediated cell signaling by the von Hippel-Lindau gene product in renal cancer. J Biol Chem. 2000;275:20700–20706
  40. Roe JS, Kim H, Lee SM, et al. p53 stabilization and transactivation by a von Hippel-Lindau protein. Mol Cell. 2006;22:395–405
  41. Nakamura E, Abreu-e-Lima P, Awakura Y, et al. Clusterin is a secreted marker for a hypoxia-inducible factor-independent function of the von Hippel-Lindau tumor suppressor protein. Am J Pathol. 2006;168:574–584
  42. Pollard PJ, El-Bahrawy M, Poulsom R, et al. Expression of HIF-1α, HIF-2α (EPAS1), and their target genes in paraganglioma and phaeochromocytoma with VHL and SDH mutations. J Clin Endocrinol Metab. 2006;[E-pub ahead of print]
  43. Ma W, Tessarollo L, Hong SB, et al. Hepatic vascular tumors, angiectasis in multiple organs, and impaired spermatogenesis in mice with conditional inactivation of the VHL gene. Cancer Res. 2003;63:5320–5328
  44. Elson DA, Thurston G, Huang LE, et al. Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1alpha. Genes Dev. 2001;15:2520–2532
  45. Kim WY, Safran M, Buckley MR, et al. Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL inactivation in vivo. EMBO J. 2006;[E-pub ahead of print]
  46. Percy MJ, Zhao Q, Flores A, et al. A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis. Proc Natl Acad Sci U S A. 2006;103:654–659
  47. Seeley TW, Langsetmo I, Stephenson R, et al. FG-2216: Tumor progression studies and correction of anemia of chronic disease in xenograft models. (meeting abstract) J Am Soc Nephrol. 2005;16:481A
  48. Gordeuk VR, Sergueeva AI, Miasnikova GY, et al. Congenital disorder of oxygen sensing: Association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors. Blood. 2004;103:3924–3932
  49. Krapf R, Beeler I, Hertner D, et al. Chronic respiratory alkalosis (The effect of sustained hyperventilation on renal regulation of acid-base equilibrium). N Engl J Med. 1991;324:1394–1401
  50. Lugliani R, Whipp BJ, Seard C, et al. Effect of bilateral carotid-body resection on ventilatory control at rest and during exercise in man. N Engl J Med. 1971;285:1105–1111
  51. Wade JG, Larson CP, Hickey RF, et al. Effect of carotid endarterectomy on carotid chemoreceptor and baroreceptor function in man. N Engl J Med. 1970;282:823–829
  52. Lahiri S, Roy A, Baby SM, et al. Oxygen sensing in the body. Prog Biophys Mol Biol. 2006;91:249–286
  53. Joseph V, Soliz J, Soria R, et al. Dopaminergic metabolism in carotid bodies and high-altitude acclimatization in female rats. Am J Physiol. 2002;282:R765–R773
  54. Hui AS, Striet JB, Gudelsky G, et al. Regulation of catecholamines by sustained and intermittent hypoxia in neuroendocrine cells and sympathetic neurons. Hypertension. 2003;42:1130–1136
  55. Baby SM, Roy A, Mokashi AM, et al. Effects of hypoxia and intracellular iron chelation on hypoxia-inducible factor-1alpha and -1beta in the rat carotid body and glomus cells. Histochem Cell Biol. 2003;120:343–352
  56. Peng YJ, Yuan G, Ramakrishnan D, et al. Heterozygous hif-1 deficiency impairs carotid body-mediated cardio-respiratory responses and ROS generation in mice exposed to chronic intermittent hypoxia. J Physiol. 2006;[E-pub ahead of print]
  57. Roy A, Li J, Baby SM, et al. Effects of iron-chelators on ion-channels and HIF-1alpha in the carotid body. Respir Physiol Neurobiol. 2004;141:115–123
  58. Schmitt P, Garcia C, Soulier V, et al. Influence of long-term hypoxia on tyrosine hydroxylase in the rat carotid body and adrenal gland. J Auton Nerv Syst. 1992;40:13–19
  59. Quik M, Sourkes TL. The effect of chronic iron deficiency on adrenal tyrosine hydroxylase activity. Can J Biochem. 1977;55:60–65
  60. Moudgil R, Michelakis ED, Archer SL. Hypoxic pulmonary vasoconstriction. J Appl Physiol. 2005;98:390–403
  61. Gruppo Italiano Studio Policitemia: Polycythemia vera: The natural history of 1213 patients followed for 20 years. Ann Intern Med. 1995;123:656–664
  62. Dingli D, Utz JP, Krowka MJ, et al. Unexplained pulmonary hypertension in chronic myeloproliferative disorders. Chest. 2001;120:801–808
  63. Garcia-Manero G, Schuster SJ, Patrick H, et al. Pulmonary hypertension in patients with myelofibrosis secondary to myeloproliferative diseases. Am J Hematol. 1999;60:130–135
  64. Kadikoylu G, Onbasili A, Tekten T, et al. Functional and morphological cardiac changes in myeloproliferative disorders (clinical study). Int J Cardiol. 2004;97:213–220
  65. Smith TG, Brooks JT, Balanos GM, et al. Mutation of von Hippel-Lindau tumour suppressor and human cardiopulmonary physiology. PLoS Med. 2006;3:e290;[E-pub ahead of print]
  66. Bushuev VI, Miasnikova GY, Sergueeva AI, et al. Endothelin-1, vascular endothelial growth factor and systolic pulmonary artery pressure in patients with Chuvash polycythemia. Haematologica. 2006;91:744–749
  67. Lee KH, Choi E, Chun YS, et al. Differential responses of two degradation domains of HIF-1alpha to hypoxia and iron deficiency. Biochimie. 2006;88:163–169
  68. Ren X, Dorrington KL, Maxwell PH, et al. Effects of desferrioxamine on serum erythropoietin and ventilatory sensitivity to hypoxia in humans. J Appl Physiol. 2000;89:680–686
  69. Balanos GM, Dorrington KL, Robbins PA. Desferrioxamine elevates pulmonary vascular resistance in humans: Potential for involvement of HIF-1. J Appl Physiol. 2002;92:2501–2507
  70. Beard J, Green W, Miller L, et al. Effect of iron-deficiency anemia on hormone levels and thermoregulation during cold exposure. Am J Physiol. 1984;247:R114–R119
  71. Turner LR, Premo DA, Gibbs BJ, et al. Adaptations to iron deficiency: Cardiac functional responsiveness to norepinephrine, arterial remodeling, and the effect of beta-blockade on cardiac hypertrophy. BMC Physiol. 2002;2:1
  72. Rossi MA, Carillo SV. Pathogenesis of cardiac hypertrophy in iron deficiency anaemia: The role of noradrenaline. Br J Exp Pathol. 1982;63:269–277
  73. Rossi MA, Carillo SV. Does norepinephrine play a central causative role in the process of cardiac hypertrophy?. Am Heart J. 1985;109:622–624
  74. Dallman PR, Goodman JR. Enlargement of mitochondrial compartment in iron and copper deficiency. Blood. 1970;35:496–505
  75. Goodman JR, Warshaw JB, Dallman PR. Cardiac hypertrophy in rats with iron and copper deficiency: Quantitative contribution of mitochondrial enlargement. Pediatr Res. 1970;4:244–256
  76. Golovin AA, Konvai VD, Red’kin IUV, et al. The external respiratory function of patients with iron-deficiency anemia and the possible mechanisms of its disorder. Ter Arkh. 1990;62:53–55
  77. Barnes PJ, Liu SF. Regulation of pulmonary vascular tone. Pharmacol Rev. 1995;47:87–131
  78. Goerre S, Wenk M, Bartsch P, et al. Endothelin-1 in pulmonary hypertension associated with high-altitude exposure. Circulation. 1995;91:359–364
  79. Johnson W, Nohria A, Garrett L, et al. Contribution of endothelin to pulmonary vascular tone under normoxic and hypoxic conditions. Am J Physiol. 2002;283:H568–H575
  80. Hoshikawa Y, Ono S, Suzuki S, et al. Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia. J Appl Physiol. 2001;90:1299–1306
  81. Fike CD, Kaplowitz MR, Pfister SL. Arachidonic acid metabolites and an early stage of pulmonary hypertension in chronically hypoxic newborn pigs. Am J Physiol. 2003;284:L316–L323
  82. Ono S, Westcott JY, Voelkel NF. PAF antagonists inhibit pulmonary vascular remodeling induced by hypobaric hypoxia in rats. J Appl Physiol. 1992;73:1084–1092
  83. Koulmann N, Novel-Chate V, Peinnequin A, et al. Cyclosporin A inhibits hypoxia-induced pulmonary hypertension and right ventricle hypertrophy. Am J Respir Crit Care Med. 2006;174:699–705
  84. Marcos E, Adnot S, Pham MH, et al. Serotonin transporter inhibitors protect against hypoxic pulmonary hypertension. Am J Respir Crit Care Med. 2003;168:487–493[E-pub 2003 May 28]
  85. Russell PC, Wright CE, Barer GR, et al. Histamine induced pulmonary vasodilatation in the rat: Site of action and changes in chronic hypoxia. Eur Respir J. 1994;7:1138–1144
  86. Chen YF, Feng JA, Li P, et al. Atrial natriuretic peptide-dependent modulation of hypoxia-induced pulmonary vascular remodeling. Life Sci. 2006;79:1357–1365
  87. Hubloue I, Rondelet B, Kerbaul F, et al. Endogenous angiotensin II in the regulation of hypoxic pulmonary vasoconstriction in anaesthetized dogs. Crit Care. 2004;8:R163–R171
  88. Quinn DA, Dahlberg CG, Bonventre JP, et al. The role of Na+/H+ exchange and growth factors in pulmonary artery smooth muscle cell proliferation. Am J Respir Cell Mol Biol. 1996;14:139–145
  89. Quinn DA, Du HK, Thompson BT, et al. Amiloride analogs inhibit chronic hypoxic pulmonary hypertension. Am J Respir Crit Care Med. 1998;157:1263–1268
  90. Rios EJ, Fallon M, Wang J, et al. Chronic hypoxia elevates intracellular pH and activates Na+/H+ exchange in pulmonary arterial smooth muscle cells. Am J Physiol. 2005;289:L867–L874
  91. Shimoda LA, Fallon M, Pisarcik S, et al. HIF-1 regulates hypoxic induction of NHE1 expression and alkalinization of intracellular pH in pulmonary arterial myocytes. Am J Physiol. 2006;291:L941–L949
  92. Yu AY, Shimoda LA, Iyer NV, et al. Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1alpha. J Clin Invest. 1999;103:691–696

PII: S0270-9295(06)00146-X

doi: 10.1016/j.semnephrol.2006.10.006

Seminars in Nephrology
Volume 26, Issue 6 , Pages 454-465 , November 2006

Article Tools

* Image Usage & Resolution