The heme oxygenase - Carbon monoxide system: Regulation and role in stress response and organ failure

Intensive Care Medicine

Volumn 34, Issue 4, 2008, Pages 640-648

  Bauer, Michael ^a   Huse, Klaus ^b   Settmacher, Utz ^a   Claus, Ralf A ^a  

^a FRIEDRICH SCHILLER UNIVERSITY JENA   (Germany)

^b FRITZ LIPMANN INSTITUTE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BILIVERDIN; CARBON MONOXIDE; FERROUS ION; HEME OXYGENASE; ISOENZYME;

ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; BIOLOGICAL ACTIVITY; BLOOD FLOW; CELL DEATH; CELL PROTECTION; CYTOTOXICITY; DNA POLYMORPHISM; ENZYME ACTIVITY; ENZYME INDUCTION; ERYTHROCYTE; EXPERIMENTAL MODEL; GENE EXPRESSION; GENE OVEREXPRESSION; GENE TARGETING; GENETIC VARIABILITY; HUMAN; HUMAN VERSUS ANIMAL COMPARISON; INTENSIVE CARE; INTRACELLULAR SPACE; ISCHEMIA; MICROSATELLITE MARKER; MOLECULAR CLONING; MULTIPLE ORGAN FAILURE; NONHUMAN; NUCLEOTIDE SEQUENCE; OXIDATIVE STRESS; PROTEIN FUNCTION; REGULATORY MECHANISM; REPERFUSION; REPERFUSION INJURY; REVIEW; RODENT; TRANSCRIPTION REGULATION; UPREGULATION;

ANIMALS; CARBON MONOXIDE; CRITICAL ILLNESS; DISEASE MODELS, ANIMAL; GENE EXPRESSION REGULATION, ENZYMOLOGIC; HEME OXYGENASE (DECYCLIZING); HEME OXYGENASE-1; HUMANS; OXIDATIVE STRESS; RODENTIA;

EID: 43349090130     PISSN: 03424642     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00134-008-1010-2     Document Type: Review

References (102)

1. Maines MD (1992) Heme oxygenase. Clinical applications and functions. CRC Press, Boca Raton, FL
2. Balla G, Vercellotti GM, Muller-Eberhard U, Eaton J, Jacob HS (1991) Exposure of endothelial cells to free heme potentiates damage mediated by granulocytes and toxic oxygen species. Lab Invest 64:648-655
3. Gutteridge JM, Smith A (1988) Antioxidant protection by haemopexin of haem-stimulated lipid peroxidation. Biochem J 256:861-865
4. Ryter SW, Tyrrell RM (2000) The heme synthesis and degradation pathways: role in oxidant sensitivity. Heme oxygenase has both pro- and antioxidant properties. Free Radic Biol Med 28:289-309
5. 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
6. Elbirt KK, Bonkovsky HL (1999) Heme oxygenase: recent advances in understanding its regulation and role. Proc Assoc Am Physicians 111:438-447
7. Kutty RK, Maines MD (1981) Purification and characterization of biliverdin reductase from rat liver. J Biol Chem 256:3956-3962
8. Maines MD (1997) The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 37:517-554
9. Suematsu M, Wakabayashi Y, Ishimura Y (1996) Gaseous monoxides: a new class of microvascular regulator in the liver. Cardiovasc Res 32:679-686
10. Naik JS, Walker BR (2003) Heme oxygenase-mediated vasodilation involves vascular smooth muscle cell hyperpolarization. Am J Physiol Heart Circ Physiol 285:H2, 20-28
11. Hosein S, Marks GS, Brien JF, McLaughlin BE, Nakatsu K (2002) An extracellular source of heme can induce a significant heme oxygenase mediated relaxation in the rat aorta. Can J Physiol Pharmacol 80:761-765
12. Zhang F, Kaide J, Wei Y, Jiang H, Yu C, Balazy M, Abraham NG, Wang W, Nasjletti A (2001) Carbon monoxide produced by isolated arterioles attenuates pressure-induced vasoconstriction. Am J Physiol Heart Circ Physiol 281:H350-358
13. Wu L, Wang R (2005) Carbon monoxide: endogenous production, physiological functions, and pharmacological applications. Pharmacol Rev 57:585-630
14. Wang R, Wu L (1997) The chemical modification of KCa channels by carbon monoxide in vascular smooth muscle cells. J Biol Chem 272:8222-8226
15. Tang XD, Xu R, Reynolds MF, Garcia ML, Heinemann SH, Hoshi T (2003) Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels. Nature 425:531-535
16. Jaggar JH, Li A, Parfenova H, Liu J, Umstot ES, Dopico AM, Leffler CW (2005) Heme is a carbon monoxide receptor for large-conductance Ca2+-activated K+ channels. Circ Res 97:805-812
17. Xi Q, Tcheranova D, Parfenova H, Horowitz B, Leffler CW, Jaggar JH (2004) Carbon monoxide activates KCa channels in newborn arteriole smooth muscle cells by increasing apparent Ca2+ sensitivity of alpha-subunits. Am J Physiol Heart Circ Physiol 286:H610-618
18. Jaggar JH, Porter VA, Lederer WJ, Nelson MT (2000) Calcium sparks in smooth muscle. Am J Physiol Cell Physiol 278:C235-256
19. Jaggar JH, Leffler CW, Cheranov SY, Tcheranova D, Shuyu E, Cheng X (2002) Carbon monoxide dilates cerebral arterioles by enhancing the coupling of Ca2+ sparks to Ca2+-activated K+ channels. Circ Res 91:610-617
20. Vreman HJ, Stevenson DK (1988) Heme oxygenase activity as measured by carbon monoxide production. Anal Biochem 168:31-38
21. Maines MD (1988) Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 2:2557-2568
22. Cruse I, Maines MD (1988) Evidence suggesting that the two forms of heme oxygenase are products of different genes. J Biol Chem 263:3348-3353
23. 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
24. Shibahara S, Muller R, Taguchi H, Yoshida T (1985) Cloning and expression of cDNA for rat heme oxygenase. Proc Natl Acad Sci USA 82:7865-7869
25. Shibahara S, Yoshizawa M, Suzuki H, Takeda K, Meguro K, Endo K (1993) Functional analysis of cDNAs for two types of human heme oxygenase and evidence for their separate regulation. J Biochem 113:214-218
26. Hayashi S, Omata Y, Sakamoto H, Higashimoto Y, Hara T, Sagara Y, Noguchi M (2004) Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene. Gene 336:241-250
27. Kutty RK, Kutty G, Rodriguez IR, Chader GJ, Wiggert B (1994) Chromosomal localization of the human heme oxygenase genes: heme oxygenase-1 (HMOX1) maps to chromosome 22q12 and heme oxygenase-2 (HMOX2) maps to chromosome 16p13.3. Genomics 20:513-516
28. Kuwano A, Ikeda H, Takeda K, Nakai H, Kondo I, Shibahara S (1994) Mapping of the human gene for inducible heme oxygenase to chromosome 22q12. Tohoku J Exp Med 172:389-392
29. Trakshel GM, Maines MD (1989) Multiplicity of heme oxygenase isozymes. HO-1 and HO-2 are different molecular species in rat and rabbit. J Biol Chem 264:1323-1328
30. Bauer I, Wanner GA, Rensing H, Alte C, Miescher EA, Wolf B, Pannen BH, Clemens MG, Bauer M (1998) Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress-exposed rat liver. Hepatology 27:829-838
31. Maines MD, Eke BC, Zhao X (1996) Corticosterone promotes increased heme oxygenase-2 protein and transcript expression in the newborn rat brain. Brain Res 722:83-94
32. Sonin NV, Garcia-Pagan JC, Nakanishi K, Zhang JX, Clemens MG (1999) Patterns of vasoregulatory gene expression in the liver response to ischemia/reperfusion and endotoxemia. Shock 11:175-179
33. Shibahara S, Muller RM, Taguchi H (1987) Transcriptional control of rat heme oxygenase by heat shock. J Biol Chem 262:12889-12892
34. Bauer I, Rensing H, Florax A, Ulrich C, Pistorius G, Redl H, Bauer M (2003) Expression pattern and regulation of heme oxygenase-1/heat shock protein 32 in human liver cells. Shock 20:116-122
35. Bauer M (2003) Heme oxygenase in liver transplantation: heme catabolism and metabolites in the search of function. Hepatology 38:286-288
36. Mayr FB, Spiel A, Leitner J, Marsik C, Germann P, Ullrich R, Wagner O, Jilma B (2005) Effects of carbon monoxide inhalation during experimental endotoxemia in humans. Am J Respir Crit Care Med 171:354-360
37. Bauer M, Bauer I (2002) Heme oxygenase-1: redox regulation and role in the hepatic response to oxidative stress. Antioxid Redox Signal 4:749-758
38. Shan Y, Lambrecht RW, Ghaziani T, Donohue SE, Bonkovsky HL (2004) Role of Bach-1 in regulation of heme oxygenase-1 in human liver cells: insights from studies with small interfering RNAS. J Biol Chem 279:51769-51774
39. Deramaudt TB, da Silva JL, Remy P, Kappas A, Abraham NG (1999) Negative regulation of human heme oxygenase in microvessel endothelial cells by dexamethasone. Proc Soc Exp Biol Med 222:185-193
40. Grosser N, Hemmerle A, Berndt G, Erdmann K, Hinkelmann U, Schurger S, Wijayanti N, Immenschuh S, Schroder H (2004) The antioxidant defense protein heme oxygenase 1 is a novel target for statins in endothelial cells. Free Radic Biol Med 37:2064-2071
41. Rensing H, Bauer I, Kubulus D, Wolf B, Winning J, Ziegeler S, Bauer M (2004) Heme oxygenase-1 gene expression in pericentral hepatocytes through beta1-adrenoceptor stimulation. Shock 21:376-387
42. Raddatz A, Kubulus D, Winning J, Bauer I, Pradarutti S, Wolf B, Kreuer S, Rensing H (2006) Dobutamine improves liver function after hemorrhagic shock through induction of heme oxygenase-1. Am J Respir Crit Care Med 174:198-207
43. Kubulus D, Rensing H, Paxian M, Thierbach JT, Meisel T, Redl H, Bauer M, Bauer I (2005) Influence of heme-based solutions on stress protein expression and organ failure after hemorrhagic shock. Crit Care Med 33:629-637
44. Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235:1043-1046
45. Suematsu M, Goda N, Sano T, Kashiwagi S, Egawa T, Shinoda Y, Ishimura Y (1995) Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver. J Clin Invest 96:2431-2437
46. Bauer M, Pannen BH, Bauer I, Herzog C, Wanner GA, Hanselmann R, Zhang JX, Clemens MG, Larsen R (1996) Evidence for a functional link between stress response and vascular control in hepatic portal circulation. Am J Physiol 271:G929-935
47. 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
48. Paxian M, Rensing H, Rickauer A, Schonhofen S, Schmeck J, Pannen BH, Bauer I, Bauer M (2001) Kupffer cells and neutrophils as paracrine regulators of the heme oxygenase-1 gene in hepatocytes after hemorrhagic shock. Shock 15:438-445
49. Rensing H, Bauer I, Peters I, Wein T, Silomon M, Jaeschke H, Bauer M (1999) Role of reactive oxygen species for hepatocellular injury and heme oxygenase-1 gene expression after hemorrhage and resuscitation. Shock 12:300-308
50. Pannen BH, Kohler N, Hole B, Bauer M, Clemens MG, Geiger KK (1998) Protective role of endogenous carbon monoxide in hepatic microcirculatory dysfunction after hemorrhagic shock in rats. J Clin Invest 102:1220-1228
51. Rensing H, Bauer I, Datene V, Patau C, Pannen BH, Bauer M (1999) Differential expression pattern of heme oxygenase-1/heat shock protein 32 and nitric oxide synthase-II and their impact on liver injury in a rat model of hemorrhage and resuscitation. Crit Care Med 27:2766-2775
52. Dennery PA, McDonagh AF, Spitz DR, Rodgers PA, Stevenson DK (1995) Hyperbilirubinemia results in reduced oxidative injury in neonatal Gunn rats exposed to hyperoxia. Free Radic Biol Med 19:395-404
53. Hayashi S, Takamiya R, Yamaguchi T, Matsumoto K, Tojo SJ, Tamatani T, Kitajima M, Makino N, Ishimura Y, Suematsu M (1999) Induction of heme oxygenase-1 suppresses venular leukocyte adhesion elicited by oxidative stress: role of bilirubin generated by the enzyme. Circ Res 85:663-671
54. Stocker R, McDonagh AF, Glazer AN, Ames BN (1990) Antioxidant activities of bile pigments: biliverdin and bilirubin. Methods Enzymol 186:301-309
55. Suttner DM, Dennery PA (1999) Reversal of HO-1 related cytoprotection with increased expression is due to reactive iron. FASEB J 13:1800-1809
56. Wennberg RP (1991) Cellular basis of bilirubin toxicity. N Y State J Med 91:493-496
57. Eisenstein RS (2000) Iron regulatory proteins and the molecular control of mammalian iron metabolism. Annu Rev Nutr 20:627-662
58. Balla J, Vercellotti GM, Jeney V, Yachie A, Varga Z, Eaton JW, Balla G (2005) Heme, heme oxygenase and ferritin in vascular endothelial cell injury. Mol Nutr Food Res 49:1030-1043
59. Dennery PA, Spitz DR, Yang G, Tatarov A, Lee CS, Shegog ML, Poss KD (1998) Oxygen toxicity and iron accumulation in the lungs of mice lacking heme oxygenase-2. J Clin Invest 101:1001-1011
60. Ryter SW, Si M, Lai CC, Su CY (2000) Regulation of endothelial heme oxygenase activity during hypoxia is dependent on chelatable iron. Am J Physiol Heart Circ Physiol 279:H2889-2897
61. Poss KD, Tonegawa S (1997) Heme oxygenase 1 is required for mammalian iron reutilization. Proc Natl Acad Sci USA 94:10919-10924
62. Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S (1999) Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest 103:129-135
63. Kawashima A, Oda Y, Yachie A, Koizumi S, Nakanishi I (2002) Heme oxygenase-1 deficiency: the first autopsy case. Hum Pathol 33:125-130
64. Ingi T, Cheng J, Ronnett GV (1996) Carbon monoxide: an endogenous modulator of the nitric oxide-cyclic GMP signaling system. Neuron 16:835-842
65. Hartsfield CL (2002) Cross talk between carbon monoxide and nitric oxide. Antioxid Redox Signal 4:301-307
66. Verma A, Hirsch DJ, Glatt CE, Ronnett GV, Snyder SH (1993) Carbon monoxide: a putative neural messenger. Science 259:381-384
67. Baranano DE, Ferris CD, Snyder SH (2001) Atypical neural messengers. Trends Neurosci 24:99-106
68. Kharitonov VG, Sharma VS, Pilz RB, Magde D, Koesling D (1995) Basis of guanylate cyclase activation by carbon monoxide. Proc Natl Acad Sci USA 92:2568-2571
69. Andrew CR, George SJ, Lawson DM, Eady RR (2002) Six- to five-coordinate heme-nitrosyl conversion in cytochrome c' and its relevance to guanylate cyclase. Biochemistry 41:2353-2360
70. Stone JR, Marletta MA (1994) Soluble guanylate cyclase from bovine lung: activation with nitric oxide and carbon monoxide and spectral characterization of the ferrous and ferric states. Biochemistry 33:5636-5640
71. Friebe A, Schultz G, Koessling D (1996) Sensitizing soluble guanylate cyclase to become a highly CO-sensitive enzyme. EMBO J 15:6835-6868
72. Xue L, Farrugia G, Miller SM, Ferris CD, Snyder SH, Szurszewski JH (2000) Carbon monoxide and nitric oxide as coneurotransmitters in the enteric nervous system: evidence from genomic deletion of biosynthetic enzymes. Proc Natl Acad Sci USA 97:1851-1855
73. Kweon MH, Park YI, Sung HC, Mukhtar H (2006) The novel antioxidant 3-O-caffeoyl-1-methylquinic acid induces Nrf2-dependent phase II detoxifying genes and alters intracellular glutathione redox. Free Radic Biol Med 40:1349-1361
74. Ryter SW, Choi AM (2002) Heme oxygenase-1: molecular mechanisms of gene expression in oxygen-related stress. Antioxid Redox Signal 4:625-632
75. Chang SH, Garcia J, Melendez JA, Kilberg MS, Agarwal A (2003) Haem oxygenase 1 gene induction by glucose deprivation is mediated by reactive oxygen species via the mitochondrial electron-transport chain. Biochem J 371:877-885
76. Suh GY, Jin Y, Yi AK, Wang XM, Choi AM (2006) CCAAT/enhancer-binding Protein Mediates Carbon Monoxide-induced Suppression of Cyclooxygenase-2. Am J Respir Cell Mol Biol 35:220-226
77. Rensing H, Bauer I, Zhang JX, Paxian M, Pannen BH, Yokoyama Y, Clemens MG, Bauer M (2002) Endothelin-1 and heme oxygenase-1 as modulators of sinusoidal tone in the stress-exposed rat liver. Hepatology 36:1453-1465
78. Sarady JK, Zuckerbraun BS, Bilban M, Wagner O, Usheva A, Liu F, Ifedigbo E, Zamora R, Choi AM, Otterbein LE (2004) Carbon monoxide protection against endotoxic shock involves reciprocal effects on iNOS in the lung and liver. FASEB J 18:854-856
79. Wang R, Wu L, Wang Z (1997) The direct effect of carbon monoxide on KCa channels in vascular smooth muscle cells. Pflugers Arch 434:285-291
80. Kaide JI, Zhang F, Wei Y, Jiang H, Yu C, Wang WH, Balazy M, Abraham NG, Nasjletti A (2001) Carbon monoxide of vascular origin attenuates the sensitivity of renal arterial vessels to vasoconstrictors. J Clin Invest 107:1163-1171
81. Tsuburai T, Suzuki M, Nagashima Y, Suzuki S, Inoue S, Hasiba T, Ueda A, Ikehara K, Matsuse T, Ishigatsubo Y (2002) Adenovirus-mediated transfer and overexpression of heme oxygenase 1 cDNA in lung prevents bleomycin-induced pulmonary fibrosis via a Fas-Fas ligand-independent pathway. Hum Gene Ther 13:1945-1960
82. Desmard M, Amara N, Lanone S, Motterlini R, Boczkowski J (2005) Carbon monoxide reduces the expression and activity of matrix metalloproteinases 1 and 2 in alveolar epithelial cells. Cell Mol Biol (Noisy-le-grand) 51:403-408
83. Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, Davis RJ, Flavell RA, Choi AM (2000) Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 6:422-428
84. Pae HO, Oh GS, Choi BM, Chae SC, Kim YM, Chung KR, Chung HAT (2004) Carbon monoxide produced by heme oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production. J Immunol 172:4744-4751
85. Poss KD, Tonegawa S (1997) Reduced stress defense in heme oxygenase 1-deficient cells. Proc Natl Acad Sci USA 94:10925-10930
86. Amersi F, Buelow R, Kato H, Ke B, Coito AJ, Shen XD, Zhao D, Zaky J, Melinek J, Lassman CR, Kolls JK, Alam J, Ritter T, Volk HD, Farmer DG, Ghobrial RM, Busuttil RW, Kupiec-Weglinski JW (1999) Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury. J Clin Invest 104:1631-1639
87. Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, Davis RJ, Flavell RA, Choi AM (2000) Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 6:422-428
88. Yu HP, Choudhry MA, Shimizu T, Hsieh YC, Schwacha MG, Yang S, Chaudry IH (2006) Mechanism of the salutary effects of flutamide on intestinal myeloperoxidase activity following trauma-hemorrhage: up-regulation of estrogen receptor-{beta}-dependent HO-1. J Leukoc Biol 79:277-284
89. Sarady-Andrews JK, Liu F, Gallo D, Nakao A, Overhaus M, Ollinger R, Choi AM, Otterbein LE (2005) Biliverdin administration protects against endotoxin-induced acute lung injury in rats. Am J Physiol Lung Cell Mol Physiol 289:L1131-1137
90. Gorbunov NV, Asher LV, Ayyagari V, Atkins JL (2006) Inflammatory leukocytes and iron turnover in experimental hemorrhagic lung trauma. Exp Mol Pathol 80:11-25
91. Akagi R, Takahashi T, Sassa S (2005) Cytoprotective effects of heme oxygenase in acute renal failure. Contrib Nephrol 148:70-85
92. Wunder C, Brock RW, Frantz S, Gottsch W, Morawietz H, Roewer N, Eichelbronner O (2005) Carbon monoxide, but not endothelin-1, plays a major role for the hepatic microcirculation in a murine model of early systemic inflammation. Crit Care Med 33:2323-2331
93. Willis D, Moore AR, Frederick R, Willoughby DA (1996) Heme oxygenase: a novel target for the modulation of the inflammatory response. Nat Med 2:87-90
94. HMOX2 locus is found in the human genome assembly hg18 at chr16:4,466,447-4,500,348
95. Texereau J, Marullo S, Hubert D, Coste J, Dusser DJ, Dall'Ava-Santucci J, Dinh-Xuan AT (2004) Nitric oxide synthase 1 as a potential modifier gene of decline in lung function in patients with cystic fibrosis. Thorax 59:156-158
96. Myers SJ, Huang Y, Genetta T, Dingledine R (2004) Inhibition of glutamate receptor 2 translation by a polymorphic repeat sequence in the 5′-untranslated leaders. J Neurosci 24:3489-3499
97. Dick P, Schillinger M, Minar E, Mlekusch W, Amighi J, Sabeti S, Schlager O, Raith M, Endler G, Mannhalter C, Wagner O, Exner M (2005) Haem oxygenase-1 genotype and cardiovascular adverse events in patients with peripheral artery disease. Eur J Clin Invest 35:731-737
98. Li P, Elrayess MA, Gomma AH, Palmen J, Hawe E, Fox KM, Humphries SE (2005) The microsatellite polymorphism of heme oxygenase-1 is associated with baseline plasma IL-6 level but not with restenosis after coronary in-stenting. Chin Med J (Engl) 118:1525-1532
99. Ullrich R, Exner M, Schillinger M, Zuckermann A, Raith M, Dunkler D, Horvat R, Grimm M, Wagner O (2005) Microsatellite polymorphism in the heme oxygenase-1 gene promoter and cardiac allograft vasculopathy. J Heart Lung Transplant 24:1600-1605
100. Li P, Sanders J, Hawe E, Brull D, Montgomery H, Humphries S (2005) Inflammatory response to coronary artery bypass surgery: does the heme-oxygenase-1 gene microsatellite polymorphism play a role? Chin Med J (Engl) 118:1285-1290
101. Geuken E, Buis CI, Visser DS, Blokzijl H, Moshage H, Nemes B, Leuvenink HG, de Jong KP, Peeters PM, Slooff MJ, Porte RJ (2005) Expression of heme oxygenase-1 in human livers before transplantation correlates with graft injury and function after transplantation. Am J Transplant 5:1875-1885
102. Exner M, Bohmig GA, Schillinger M, Regele H, Watschinger B, Horl WH, Raith M, Mannhalter C, Wagner OF (2004) Donor heme oxygenase-1 genotype is associated with renal allograft function. Transplantation 77:538-542