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Heme Oxygenase and Acute Lung Injury: The Functional Significance of Heme Oxygenase Induction

  • N. J. Lamb
  • G. J. Quinlan
  • T. W. Evans
Conference paper
Part of the Yearbook of Intensive Care and Emergency Medicine book series (YEARBOOK, volume 1999)

Abstract

In spite of major advances in intensive care, the morbidity and mortality of patients with acute respiratory distress syndrome (ARDS) remains high, and therapy is at best supportive [1, 2]. ARDS is characterized by refractory hypoxemia secondary to non-hydrostatic pulmonary edema [3] and is precipitated by a range of common predisposing factors not necessarily related to primary lung injury, such as polytrauma, severe burns, sepsis, gastric aspiration, surgery necessitating cardiopulmonary bypass (CPB), lung resection, hemorrhagic shock, and oxygen toxicity [4].

Keywords

Acute Lung Injury Acute Respiratory Distress Syndrome Heme Oxygenase Pulmonary Artery Smooth Muscle Cell Heme Oxygenase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Abel SJ, Finney SJ, Brett SJ, Keogh BF, Morgan CJ, Evans TW (1998) Reduced mortality in association with the acute respiratory distress syndrome. Thorax 53:292–294.PubMedCrossRefGoogle Scholar
  2. 2.
    Cawley MT, Skaar DJ, Anderson HL 3rd, Hanson CW 3rd (1998) Mechanical ventilation and pharmacologic strategies for acute respiratory distress syndrome. Pharmacotherapy 18:140–155.PubMedGoogle Scholar
  3. 3.
    Bernard GR, Artigas A, Brigham KL, et al (1994) The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149:818–824.PubMedGoogle Scholar
  4. 4.
    Macnaughton PD, Evans TW (1992) Management of adult respiratory distress syndrome. Lancet 22:469–472.CrossRefGoogle Scholar
  5. 5.
    Pittet JF, Mackersie RC, Martin TR, Matthay MA (1997) Biological markers of acute lung injury: prognostic and pathogenetic significance. Am J Respir Crit Care Med 155:1187–1205.PubMedGoogle Scholar
  6. 6.
    Quinlan GJ, Lamb NJ, Evans TW, Gutteridge JM (1996) Plasma fatty acid changes and increased lipid peroxidation in patients with adult respiratory distress syndrome. Crit Care Med 24:241–246.PubMedCrossRefGoogle Scholar
  7. 7.
    Quinlan GJ, Evans TW, Gutteridge JM (1994) Oxidative damage to plasma proteins in adult respiratory distress syndrome. Free Radic Res 20:289–298.PubMedCrossRefGoogle Scholar
  8. 8.
    Lamb NJ, Gutteridge JM, Evans TW, Baker C, Quinlan J (1999) Oxidative damage to proteins of bronchoalveolar lavage fluid in patients with ARDS. Evidence for neutrophil mediated hydrox-ylation, nitration and chlorination. Crit Care Med (in press).Google Scholar
  9. 9.
    Leff JA, Parsons PE, Day CE, et al (1992) Increased serum catalase activity in septic patients with the adult respiratory distress syndrome. Am Rev Respir Dis 146:985–989.PubMedGoogle Scholar
  10. 10.
    Tenhunen R, Marver HS, Schmid R (1968) The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci USA 61:748–755.PubMedCrossRefGoogle Scholar
  11. 11.
    Hartl FU, Martin J, Neupert W (1992) Protein folding in the cell: the role of molecular chaperones Hsp70 and Hsp60. Annu Rev Biophys Biomol Struct 21:293–322.PubMedCrossRefGoogle Scholar
  12. 12.
    Li GC, Werb Z (1982) Correlation between synthesis of heat shock proteins and development of thermotolerance in Chinese hamster fibroblasts. Proc Natl Acad Sci USA 79:3218–3222.PubMedCrossRefGoogle Scholar
  13. 13.
    Schroder H, Langer T, Hartl FU, Bukau B (1993) DnaK, DnaJ and GrpE form a cellular chaperone machinery capable of repairing heat-induced protein damage. EMBO J 12:4137–4144.PubMedGoogle Scholar
  14. 14.
    McCoubrey WK Jr, Huang TJ, Maines MD (1997) Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur J Biochem 247:725–732.PubMedCrossRefGoogle Scholar
  15. 15.
    Maines MD, Kappas A (1974) Cobalt induction of hepatic heme oxygenase; with evidence that cytochrome P-450 is not essential for this enzyme activity. Proc Natl Acad Sci USA 171:4293–4297.CrossRefGoogle Scholar
  16. 16.
    Maines MD, Trakshel GM, Kutty RK (1986) Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. J Biol Chem 261:411–419.PubMedGoogle Scholar
  17. 17.
    Trakshel GM, Kutty RK, Maines MD (1986) Purification and characterization of the major constitutive form of testicular heme oxygenase. The noninducible isoform. J Biol Chem 261:11131–11137.PubMedGoogle Scholar
  18. 18.
    McCoubrey WK Jr, Huang TJ, Maines MD (1997) Heme oxygenase-2 is a hemoprotein and binds heme through heme regulatory motifs that are not involved in heme catalysis. J Biol Chem 272:12568–12574.PubMedCrossRefGoogle Scholar
  19. 19.
    Yoshida T, Biro P, Cohen T, Müller RM, Shibahara S (1988) Human heme oxygenase cDNA and induction of its mRNA by hemin. Eur J Biochem 171:457–461.PubMedCrossRefGoogle Scholar
  20. 20.
    Tenhunen R, Marver HS, Schmid R (1969) The enzymatic conversion of hemoglobin to bilirubin. Trans Assoc Am Physicians 82:363–371.PubMedGoogle Scholar
  21. 21.
    Yoshida T, Kikuchi G (1978) Features of the reaction of heme degradation catalyzed by the reconstituted microsomal heme oxygenase system. J Biol Chem 253:4230–4236.PubMedGoogle Scholar
  22. 22.
    Yoshida T, Noguchi M, Kikuchi G (1980) Oxygenated form of heme/heme oxygenase complex and requirement for second electron to initiate heme degradation from the oxygenated complex. J Biol Chem 255:4418–4420.PubMedGoogle Scholar
  23. 23.
    Yoshida T, Noguchi M, Kikuchi G (1982) The step of carbon monoxide liberation in the sequence of heme degradation catalyzed by the reconstituted microsomal heme oxygenase system. J Biol Chem 257:9345–9348.PubMedGoogle Scholar
  24. 24.
    Zakhary R, Gaine SP, Dinerman JL, Ruat M, Flavahan NA, Snyder SH (1996) Heme oxygenase 2: endothelial and neuronal localization and role in endothelium-dependent relaxation. Proc Natl Acad Sci USA 93:795–798.PubMedCrossRefGoogle Scholar
  25. 25.
    Canning BJ, Fischer A (1998) Localization of heme oxygenase-2 immunoreactivity to parasympathetic ganglia of human and guinea-pig airways. Am J Respir Cell Mol Biol 18:279–285.PubMedGoogle Scholar
  26. 26.
    Choi AM, Alam J (1996) Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. Am J Respir Cell Mol Biol 15:9–19.PubMedGoogle Scholar
  27. 27.
    Keyse SM, Tyrrell RM (1989) Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad Sci USA 86:99–103.PubMedCrossRefGoogle Scholar
  28. 28.
    Applegate LA, Luscher P, Tyrrell RM (1991) Induction of heme oxygenase: a general response to oxidant stress in cultured mammalian cells. Cancer Res 51:974–978.PubMedGoogle Scholar
  29. 29.
    Vile GF, Basu-Modak S, Waltner C, Tyrrell RM (1994) Heme oxygenase 1 mediates an adaptive response to oxidative stress in human skin fibroblasts. Proc Natl Acad Sci USA 91:2607–2610.PubMedCrossRefGoogle Scholar
  30. 30.
    Alam J, Camhi S, Choi AM (1995) Identification of a second region upstream of the mouse heme oxygenase-1 gene that functions as a basal level and inducer-dependent transcription enhancer. J Biol Chem 270:11977–11984.PubMedCrossRefGoogle Scholar
  31. 31.
    Camhi SL, Alam J, Otterbein L, Sylvester SL, Choi AM (1995) Induction of heme oxygenase-1 gene expression by lipopolysaccharide is mediated by AP-1 activation. Am J Respir Cell Mol Biol 13:387–398.PubMedGoogle Scholar
  32. 32.
    Prestera T, Talalay P, Alam J, Ahn YI, Lee PJ, Choi AM (1995) Parallel induction of heme oxygenase-1 and chemoprotective phase 2 enzymes by electrophiles and antioxidants: regulation by upstream antioxidant-responsive elements (ARE). Mol Med 1:827–837.PubMedGoogle Scholar
  33. 33.
    Lee PJ, Alam J, Sylvester SL, Inamdar N, Otterbein L, Choi AM (1996) Regulation of heme oxygenase-1 expression in vivo and in vitro in hyperoxic lung injury. Am J Respir Cell Mol Biol 14:556–568.PubMedGoogle Scholar
  34. 34.
    Maines MD (1997) The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 37:517–554.PubMedCrossRefGoogle Scholar
  35. 35.
    Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235:1043–1046.PubMedCrossRefGoogle Scholar
  36. 36.
    Weiss G, Werner-Felmayer G, Werner ER, Grunewald K, Wachter H, Hentze MW (1994) Iron regulates nitric oxide synthase activity by controlling nuclear transcription. J Exp Med 180:969–976.PubMedCrossRefGoogle Scholar
  37. 37.
    Gutteridge JM (1987) The antioxidant activity of haptoglobin towards hemoglobin-stimulated lipid peroxidation. Biochim Biophys Acta 917:219–223.PubMedCrossRefGoogle Scholar
  38. 38.
    Gutteridge JM, Smith A (1988) Antioxidant protection by haemopexin of haem-stimulated lipid peroxidation. Biochem J 256:861–865.PubMedGoogle Scholar
  39. 39.
    Balla G, Jacob HS, Balla J, et al (1992) Ferritin: a cytoprotective antioxidant strategem of endothelium. J Biol Chem 267:18148–18153.PubMedGoogle Scholar
  40. 40.
    Nath KA, Balla G, Vercellotti GM, et al (1992) Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat. J Clin Invest 90:267–270.PubMedCrossRefGoogle Scholar
  41. 41.
    Vile GF, Tyrrell RM (1993) Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to a heme oxygenase-dependent increase in ferritin. J Biol Chem 268:14678–14681.PubMedGoogle Scholar
  42. 42.
    Llesuy SF, Tomaro ML (1994) Heme oxygenase and oxidative stress. Evidence of involvement of bilirubin as physiological protector against oxidative damage. Biochim Biophys Acta 1223:9–14.PubMedCrossRefGoogle Scholar
  43. 43.
    Halliwell B, Gutteridge JM (1985) Free radicals in biology and medicine. Oxford University Press, Oxford.Google Scholar
  44. 44.
    Lamb NJ, Quinlan GJ, Evans TW, Gutteridge JM (1998) Evidence for pro-oxidant activity of heme oxygenase. Intensive Care Med 24 (suppl 1): 130 (Abst).Google Scholar
  45. 45.
    Lamb NJ, Quinlan GJ, Jourdan KB, Mitchell JA, Gutteridge JM, Evans TW (1998) Increase in intracellular free iron in rat pulmonary artery smooth muscle cells on addition of heme: evidence for the pro-oxidant action of heme oxygenase. Am J Respir Crit Care Med 157:890 (Abst).Google Scholar
  46. 46.
    Maines MD, Kappas A (1978) Prematurely evoked synthesis and induction of delta-aminolevulinate synthetase in neonatal liver. Evidence for metal ion repression of enzyme formation. J Biol Chem 253:2321–2326.PubMedGoogle Scholar
  47. 47.
    Yee EL, Pitt BR, Billiar TR, Kim YM (1996) Effect of nitric oxide on heme metabolism in pulmonary artery endothelial cells. Am J Physiol 271:L512–L518.PubMedGoogle Scholar
  48. 48.
    Abraham NG, Lavrovsky Y, Schwartzman ML, et al (1995) Transfection of the human heme oxygenase gene into rabbit coronary microvessel endothelial cells: protective effect against heme and hemoglobin toxicity. Proc Natl Acad Sci USA 92:6798–6802.PubMedCrossRefGoogle Scholar
  49. 49.
    Balla J, Jacob HS, Balla G, Nath K, Eaton JW, Vercellotti GM (1993) Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage. Proc Natl Acad Sci USA 90:9285–9289.PubMedCrossRefGoogle Scholar
  50. 50.
    Balla J, Nath KA, Balla G, Juckett MB, Jacob HS, Vercellotti GM (1995) Endothelial cell heme oxygenase and ferritin induction in rat lung by hemoglobin in vivo. Am J Physiol 268:L321–L327.PubMedGoogle Scholar
  51. 51.
    Choi AM, Knobil K, Otterbein SL, Eastman DA, Jacoby DB (1996) Oxidant stress responses in influenza virus pneumonia: gene expression and transcription factor activation. Am J Physiol 271:L383–L391.PubMedGoogle Scholar
  52. 52.
    Keyse SM, Applegate LA, Tromvoukis Y, Tyrrell RM (1990) Oxidant stress leads to transcriptional activation of the human heme oxygenase gene in cultured skin fibroblasts. Mol Cell Biol 10:4967–4969.PubMedGoogle Scholar
  53. 53.
    Otterbein L, Sylvester SL, Choi AM (1995) Hemoglobin provides protection against lethal endotoxemia in rats: the role of heme oxygenase-1. Am J Respir Cell Mol Biol 13:595–601.PubMedGoogle Scholar
  54. 54.
    Lee PJ, Alam J, Wiegand GW, Choi AM (1996) Overexpression of heme oxygenase-1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia. Proc Natl Acad Sci USA 93:10393–10398.PubMedCrossRefGoogle Scholar
  55. 55.
    Murray AW (1993) Cell cycle. Sunburnt fission yeast. Nature 363:302.PubMedCrossRefGoogle Scholar
  56. 56.
    Lee PJ, Jiang BH, Chin BY, et al (1997) Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia. J Biol Chem 272:5375–5381.PubMedCrossRefGoogle Scholar
  57. 57.
    Anning PB, Chen Y, Lamb NJ, et al (1999) Tissue specific, time dependent upregulation of heme oxygenase 1 (HO-1) in iron-overloaded rats. Shock (in press).Google Scholar
  58. 58.
    Gutteridge JM, Mumby S, Quinlan GJ, Chung KF, Evans TW (1996) Pro-oxidant iron is present in human pulmonary epithelial lining fluid: implications for oxidative stress in the lung. Biochem Biophys Res Commun 220:1024–1027.PubMedCrossRefGoogle Scholar
  59. 59.
    Polla BS, Kantengwa S, Gleich GJ, Kondo M, Reimert CM, Junod AF (1993) Spontaneous heat shock protein synthesis by alveolar macrophages in interstitial lung disease associated with phagocytosis of eosinophils. Eur Respir J 6:483–488.PubMedGoogle Scholar
  60. 60.
    Meyer J, Prien T, Van Aken H, et al (1998) Arterio-venous carboxyhemoglobin difference suggests carbon monoxide production by human lungs. Biochem Biophys Res Commun 244:230–232.PubMedCrossRefGoogle Scholar
  61. 61.
    Zayasu K, Sekizawa K, Okinaga S, Yamaya M, Ohrui T, Sasaki H (1997) Increased carbon monoxide in exhaled air of asthmatic patients. Am J Respir Crit Care Med 156:1140–1143.PubMedGoogle Scholar
  62. 62.
    Nutter LM, Sierra EE, Ngo EO (1994) Heme oxygenase does not protect human cells against oxidant stress. J Lab Clin Med 123:506–514.PubMedGoogle Scholar
  63. 63.
    Carraway MS, Ghio AJ, Taylor JL, Piantadosi CA (1998) Induction of ferritin and heme oxygenase-1 by endotoxin in the lung. Am J Physiol 275:L583–L592.PubMedGoogle Scholar
  64. 64.
    Taylor JL, Carraway MS, Piantadosi CA (1998) Lung-specific induction of heme oxygenase-1 and hyperoxic lung injury. Am J Physiol 274:L582–L590.PubMedGoogle Scholar
  65. 65.
    Takahashi Y, Takahashi S, Yoshimi T, Miura T, Mochitate K, Kobayashi T (1997) Increases in the mRNA levels of gamma-glutamyltransferase and heme oxygenase-1 in the rat lung after ozone exposure. Biochem Pharmacol 53:1061–1064.PubMedCrossRefGoogle Scholar
  66. 66.
    Poss KD, Tonegawa S (1997) Heme oxygenase 1 is required for mammalian iron reutilization. Proc Natl Acad Sci USA 94:10919–10924.PubMedCrossRefGoogle Scholar
  67. 67.
    Poss KD, Tonegawa S (1997) Reduced stress defense in heme oxygenase 1-deficient cells. Proc Natl Acad Sci USA 94:10925–10930.PubMedCrossRefGoogle Scholar
  68. 68.
    Dennery PA, Spitz DR, Yang G, et al (1998) Oxygen toxicity and iron accumulation in the lungs of mice lacking heme oxygenase-2. J Clin Invest 101:1001–1011.PubMedCrossRefGoogle Scholar
  69. 69.
    Dennery PA, Yang G, Tatarov A, Poss KD, Stanford CA (1998) Decreased markers of oxidative injury after hyperoxia in the absence of lung heme oxygenase-1 in vivo. Am J Respir Crit Care Med 157:891 (Abst).Google Scholar
  70. 70.
    Dennery PA, Sridhar KJ, Lee CS, et al (1997) Heme oxygenase-mediated resistance to oxygen toxicity in hamster fibroblasts. J Biol Chem 272:14937–14942.PubMedCrossRefGoogle Scholar
  71. 71.
    Maines MD, Trakshel (1992) Differential regulation of heme oxygenase isozymes by Sn-and Znprotoporphyrins: possible relevance to suppression of hyperbilirubinemia. Biochim Biophys Acta 1131:166–174.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • N. J. Lamb
  • G. J. Quinlan
  • T. W. Evans

There are no affiliations available

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