Table of Contents Author Guidelines Submit a Manuscript
International Journal of Hypertension
Volume 2012, Article ID 859235, 19 pages
http://dx.doi.org/10.1155/2012/859235
Review Article

Therapeutic Potential of Heme Oxygenase-1/Carbon Monoxide in Lung Disease

1Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA
2College of Arts and Sciences, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA
3Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA

Received 14 August 2011; Accepted 6 October 2011

Academic Editor: David E. Stec

Copyright © 2012 Myrna Constantin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. B. Wu, C. Hunt, and R. Morimoto, “Structure and expression of the human gene encoding major heat shock protein HSP70,” Molecular and Cellular Biology, vol. 5, no. 2, pp. 330–341, 1985. View at Google Scholar · View at Scopus
  2. R. P. Beckmann, L. A. Mizzen, and W. J. Welch, “Interaction of Hsp 70 with newly synthesized proteins: implications for protein folding and assembly,” Science, vol. 248, no. 4957, pp. 850–854, 1990. View at Google Scholar · View at Scopus
  3. G. C. Li and Z. Werb, “Correlation between synthesis of heat shock proteins and development of thermotolerance in Chinese hamster fibroblasts,” Proceedings of the National Academy of Sciences of the United States of America, vol. 79, no. 10, pp. 3218–3222, 1982. View at Google Scholar · View at Scopus
  4. S. M. Keyse and R. M. Tyrrell, “Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite,” Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 1, pp. 99–103, 1989. View at Google Scholar · View at Scopus
  5. S. M. Keyse and R. M. Tyrrell, “Both near ultraviolet radiation and the oxidizing agent hydrogen peroxide induce a 32-kDa stress protein in normal human skin fibroblasts,” The Journal of Biological Chemistry, vol. 262, no. 30, pp. 14821–14825, 1987. View at Google Scholar · View at Scopus
  6. L. A. Applegate, P. Luscher, and R. M. Tyrrell, “Induction of heme oxygenase: a general response to oxidant stress in cultured mammalian cells,” Cancer Research, vol. 51, no. 3, pp. 974–978, 1991. View at Google Scholar · View at Scopus
  7. M. Rizzardini, M. Terao, F. Falciani, and L. Cantoni, “Cytokine induction of haem oxygenase mRNA in mouse liver: interleukin 1 transcriptionally activates the haem oxygenase gene,” Biochemical Journal, vol. 290, no. 2, pp. 343–347, 1993. View at Google Scholar · View at Scopus
  8. C. M. Terry, J. A. Clikeman, J. R. Hoidal, and K. S. Callahan, “Effect of tumor necrosis factor-α and interleukin-1α on heme oxygenase-1 expression in human endothelial cells,” American Journal of Physiology, vol. 274, no. 3, pp. H883–H891, 1998. View at Google Scholar · View at Scopus
  9. S. L. Camhi, J. Alam, L. Otterbein, S. L. Sylvester, and A. M. Choi, “Induction of heme oxygenase-1 gene expression by lipopolysaccharide is mediated by AP-1 activation,” American Journal of Respiratory Cell and Molecular Biology, vol. 13, no. 4, pp. 387–398, 1995. View at Google Scholar · View at Scopus
  10. S. L. Camhi, J. Alam, G. W. Wiegand, B. Y. Chin, and A. M. K. Choi, “Transcriptional activation of the HO-1 gene by lipopolysaccharide is mediated by 5′ distal enhancers: role of reactive oxygen intermediates and AP-1,” American Journal of Respiratory Cell and Molecular Biology, vol. 18, no. 2, pp. 226–234, 1998. View at Google Scholar · View at Scopus
  11. R. Tenhunen, H. S. Marver, and R. Schmid, “Microsomal heme oxygenase. Characterization of the enzyme,” The Journal of Biological Chemistry, vol. 244, no. 23, pp. 6388–6394, 1969. View at Google Scholar · View at Scopus
  12. D.B. Menzel and M.O. Amdur, “Toxic response of the respiratory system,” in Casarett & Doull's Toxicology: The Basic Science of Poisons, K. Klaassen, M. O. Amdur, and J. Doull, Eds., pp. 330–358, MacMillan, New York, NY, USA, 3rd edition, 1986. View at Google Scholar
  13. L. E. Otterbein, J. K. Kolls, L. L. Mantell, J. L. Cook, J. Alam, and A. M. K. Choi, “Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury,” Journal of Clinical Investigation, vol. 103, no. 7, pp. 1047–1054, 1999. View at Google Scholar · View at Scopus
  14. T. Hashiba, M. Suzuki, Y. Nagashima et al., “Adenovirus-mediated transfer of heme oxygenase-1 cDNA attenuates severe lung injury induced by the influenza virus in mice,” Gene Therapy, vol. 8, no. 19, pp. 1499–1507, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. S. Inoue, M. Suzuki, Y. Nagashima et al., “Transfer of heme oxygenase 1 cDNA by a replication-deficient adenovirus enhances interleukin 10 production from alveolar macrophages that attenuates lipopolysaccharide-induced acute lung injury in mice,” Human Gene Therapy, vol. 12, no. 8, pp. 967–979, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. H. J. Duckers, M. Boehm, A. L. True et al., “Heme oxygenase-1 protects against vascular constriction and proliferation,” Nature Medicine, vol. 7, no. 6, pp. 693–698, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. H. Christou, T. Morita, C. M. Hsieh et al., “Prevention of hypoxia-induced pulmonary hypertension by enhancement of endogenous heme oxygenase-1 in the rat,” Circulation Research, vol. 86, no. 12, pp. 1224–1229, 2000. View at Google Scholar · View at Scopus
  18. T. Minamino, H. Christou, C. M. Hsieh et al., “Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 15, pp. 8798–8803, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. S. H. Juan, T. S. Lee, K. W. Tseng et al., “Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein e-deficient mice,” Circulation, vol. 104, no. 13, pp. 1519–1525, 2001. View at Google Scholar · View at Scopus
  20. K. Ishikawa, D. Sugawara, X. P. Wang et al., “Heme oxygenase-1 inhibits atherosclerotic lesion formation in LDL-receptor knockout mice,” Circulation Research, vol. 88, no. 5, pp. 506–512, 2001. View at Google Scholar · View at Scopus
  21. S. W. Ryter, J. Alam, and A. M. K. Choi, “Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications,” Physiological Reviews, vol. 86, no. 2, pp. 583–650, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. L. E. Otterbein, F. H. Bach, J. Alam et al., “Carbon monoxide has anti-inflammatory effects involving the mitogen- activated protein kinase pathway,” Nature Medicine, vol. 6, no. 4, pp. 422–428, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. L. E. Otterbein, L. L. Mantell, and A. M. K. Choi, “Carbon monoxide provides protection against hyperoxic lung injury,” American Journal of Physiology, vol. 276, no. 4, pp. L688–L694, 1999. View at Google Scholar · View at Scopus
  24. P. Sawle, R. Foresti, B. E. Mann, T. R. Johnson, C. J. Green, and R. Motterlini, “Carbon monoxide-releasing molecules (CO-RMs) attenuate the inflammatory response elicited by lipopolysaccharide in RAW264.7 murine macrophages,” British Journal of Pharmacology, vol. 145, no. 6, pp. 800–810, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. R. Motterlini and L. E. Otterbein, “The therapeutic potential of carbon monoxide,” Nature Reviews Drug Discovery, vol. 9, no. 9, pp. 728–743, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. C. Fondevila, X. D. Shen, S. Tsuchiyashi et al., “Biliverdin therapy protects rat livers from ischemia and reperfusion injury,” Hepatology, vol. 40, no. 6, pp. 1333–1341, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. A. Nakao, N. Murase, C. Ho, H. Toyokawa, T. R. Billiar, and S. Kanno, “Biliverdin administration prevents the formation of intimal hyperplasia induced by vascular injury,” Circulation, vol. 112, no. 4, pp. 587–591, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. R. Öllinger, M. Bilban, A. Erat et al., “A natural inhibitor of vascular smooth muscle cell proliferation,” Circulation, vol. 112, no. 7, pp. 1030–1039, 2005. View at Publisher · View at Google Scholar · View at PubMed
  29. S. Brouard, L. E. Otterbein, J. Anrather et al., “Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis,” Journal of Experimental Medicine, vol. 192, no. 7, pp. 1015–1025, 2000. View at Publisher · View at Google Scholar · View at Scopus
  30. R. Song, Z. Zhou, P. K. M. Kim et al., “Carbon monoxide promotes Fas/CD95-induced apoptosis in Jurkat cells,” The Journal of Biological Chemistry, vol. 279, no. 43, pp. 44327–44334, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. T. Morita, S. A. Mitsialis, H. Koike, Y. Liu, and S. Kourembanas, “Carbon monoxide controls the proliferation of hypoxic vascular smooth muscle cells,” The Journal of Biological Chemistry, vol. 272, no. 52, pp. 32804–32809, 1997. View at Publisher · View at Google Scholar · View at Scopus
  32. L. E. Otterbein, B. S. Zuckerbraun, M. Haga et al., “Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury,” Nature Medicine, vol. 9, no. 2, pp. 183–190, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. H. P. Kim, X. Wang, A. Nakao et al., “Caveolin-1 expression by means of p38β mitogen-activated protein kinase mediates the antiproliferative effect of carbon monoxide,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 32, pp. 11319–11324, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. B. S. Zuckerbraun, Y. C. Beek, B. Wegiel et al., “Carbon monoxide reverses established pulmonary hypertension,” Journal of Experimental Medicine, vol. 203, no. 9, pp. 2109–2119, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. K. D. Poss and S. Tonegawa, “Heme oxygenase 1 is required for mammalian iron reutilization,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 20, pp. 10919–10924, 1997. View at Publisher · View at Google Scholar · View at Scopus
  36. M. D. Maines and A. Kappas, “Cobalt induction of hepatic heme oxygenase; with evidence that cytochrome P 450 is not essential for this enzyme activity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 71, no. 11, pp. 4293–4297, 1974. View at Google Scholar · View at Scopus
  37. F. P. Guengerich, D. P. Ballou, and M. J. Coon, “Purified liver microsomal cytochrome P 450. Electron accepting properties and oxidation reduction potential,” The Journal of Biological Chemistry, vol. 250, no. 18, pp. 7405–7414, 1975. View at Google Scholar · View at Scopus
  38. T. Yoshida, M. Noguchi, and G. Kikuchi, “Oxygenated form of heme . heme oxygenase complex and requirement for second electron to initiate heme degradation from the oxygenated complex,” The Journal of Biological Chemistry, vol. 255, no. 10, pp. 4418–4420, 1980. View at Google Scholar · View at Scopus
  39. T. Yoshinaga, S. Sassa, and A. Kappas, “The occurrence of molecular interactions among NADPH-cytochrome c reductase, heme oxygenase, and biliverdin reductase in heme degradation,” The Journal of Biological Chemistry, vol. 257, no. 13, pp. 7786–7793, 1982. View at Google Scholar · View at Scopus
  40. M. Noguchi, T. Yoshida, and G. Kikuchi, “Specific requirement of NADPH-cytochrome c reductase for the microsomal heme oxygenase reaction yielding biliverdin IXα,” FEBS Letters, vol. 98, no. 2, pp. 281–284, 1979. View at Google Scholar · View at Scopus
  41. T. Yoshida and G. Kikuchi, “Features of the reaction of heme degradation catalyzed by the reconstituted microsomal heme oxygenase system,” The Journal of Biological Chemistry, vol. 253, no. 12, pp. 4230–4236, 1978. View at Google Scholar · View at Scopus
  42. G. Kikuchi and T. Yoshida, “Heme catabolism by the reconstituted heme oxygenase system,” Annals of Clinical Research, vol. 8, no. 17, pp. 10–17, 1976. View at Google Scholar · View at Scopus
  43. T. Yoshida and G. Kikuchi, “Sequence of the reaction of heme catabolism catalyzed by the microsomal heme oxygenase system,” FEBS Letters, vol. 48, no. 2, pp. 256–261, 1974. View at Publisher · View at Google Scholar · View at Scopus
  44. R. Tenhunen, M. E. Ross, H. S. Marver, and R. Schmid, “Reduced nicotinamide-adenine dinucleotide phosphate dependent biliverdin reductase: partial purification and characterization,” Biochemistry, vol. 9, no. 2, pp. 298–303, 1970. View at Google Scholar · View at Scopus
  45. R. Stocker, Y. Yamamoto, A. F. McDonagh, A. N. Glazer, and B. N. Ames, “Bilirubin is an antioxidant of possible physiological importance,” Science, vol. 235, no. 4792, pp. 1043–1046, 1987. View at Google Scholar · View at Scopus
  46. R. Stocker, A. N. Glazer, and B. N. Ames, “Antioxidant activity of albumin-bound bilirubin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 84, no. 16, pp. 5918–5922, 1987. View at Google Scholar · View at Scopus
  47. C. D. King, G. R. Rios, M. D. Green, and T. R. Tephly, “UDP-Glucuronosyltransferases,” Current Drug Metabolism, vol. 1, no. 2, pp. 143–161, 2000. View at Google Scholar · View at Scopus
  48. M. D. Maines, G. M. Trakshel, and R. K. Kutty, “Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible,” The Journal of Biological Chemistry, vol. 261, no. 1, pp. 411–419, 1986. View at Google Scholar · View at Scopus
  49. M. D. Maines, “The heme oxygenase system: a regulator of second messenger gases,” Annual Review of Pharmacology and Toxicology, vol. 37, pp. 517–554, 1997. View at Google Scholar · View at Scopus
  50. L. A. Applegate, P. Luscher, and R. M. Tyrrell, “Induction of heme oxygenase: a general response to oxidant stress in cultured mammalian cells,” Cancer Research, vol. 51, no. 3, pp. 974–978, 1991. View at Google Scholar · View at Scopus
  51. R. Tenhunen, H. S. Marver, and R. Schmid, “The enzymatic catabolism of hemoglobin: stimulation of microsomal heme oxygenase by hemin,” The Journal of Laboratory and Clinical Medicine, vol. 75, no. 3, pp. 410–421, 1970. View at Google Scholar · View at Scopus
  52. V. S. Raju and M. D. Maines, “Coordinated expression and mechanism of induction of HSP32 (heme oxygenase-1) mRNA by hyperthermia in rat organs,” Biochimica et Biophysica Acta, vol. 1217, no. 3, pp. 273–280, 1994. View at Publisher · View at Google Scholar · View at Scopus
  53. I. Cruse and M. D. Maines, “Evidence suggesting that the two forms of heme oxygenase are products of different genes,” The Journal of Biological Chemistry, vol. 263, no. 7, pp. 3348–3353, 1988. View at Google Scholar · View at Scopus
  54. G. M. Trakshel, R. K. Kutty, and M. D. Maines, “Purification and characterization of the major constitutive form of testicular heme oxygenase. The noninducible isoform,” The Journal of Biological Chemistry, vol. 261, no. 24, pp. 11131–11137, 1986. View at Google Scholar · View at Scopus
  55. W. K. McCoubrey, T. J. Huang, and M. D. Maines, “Heme oxygenase-2 is a hemoprotein and binds heme through heme regulatory motifs that are not involved in heme catalysis,” The Journal of Biological Chemistry, vol. 272, no. 19, pp. 12568–12574, 1997. View at Publisher · View at Google Scholar · View at Scopus
  56. M. D. Maines, B. C. Eke, and X. Zhao, “Corticosterone promotes increased heme oxygenase-2 protein and transcript expression in the newborn rat brain,” Brain Research, vol. 722, no. 1-2, pp. 83–94, 1996. View at Publisher · View at Google Scholar · View at Scopus
  57. V. S. Raju, W. K. McCoubrey, and M. D. Maines, “Regulation of heme oxygenase-2 by glucocorticoids in neonatal rat brain: characterization of a functional glucocorticoid response element,” Biochimica et Biophysica Acta, vol. 1351, no. 1-2, pp. 89–104, 1997. View at Publisher · View at Google Scholar · View at Scopus
  58. P. J. Lee, J. Alam, G. W. Wiegand, and A. M. K. Choi, “Overexpression of heme oxygenase-1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 19, pp. 10393–10398, 1996. View at Publisher · View at Google Scholar · View at Scopus
  59. I. Petrache, L. E. Otterbein, J. Alam, G. W. Wiegand, and A. M. K. Choi, “Heme oxygenase-1 inhibits TNF-α-induced apoptosis in cultured fibroblasts,” American Journal of Physiology, vol. 278, no. 2, pp. L312–L319, 2000. View at Google Scholar · View at Scopus
  60. G. Carlin, R. Djursäter, and K. E. Arfors, “Inhibition of heme-promoted enzymatic lipid peroxidation by desferrioxamine and EDTA,” Upsala Journal of Medical Sciences, vol. 93, no. 3, pp. 215–223, 1988. View at Google Scholar · View at Scopus
  61. A. L. Tappel, “The mechanism of the oxidation of unsaturated fatty acids catalyzed by hematin compounds,” Archives of Biochemistry and Biophysics, vol. 44, no. 2, pp. 378–395, 1953. View at Google Scholar · View at Scopus
  62. J. Balla, H. S. Jacob, G. Balla, K. Nath, J. W. Eaton, and G. M. Vercellotti, “Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 20, pp. 9285–9289, 1993. View at Publisher · View at Google Scholar · View at Scopus
  63. D. M. Suttner and P. A. Dennery, “Reversal of HO-1 related cytoprotection with increased expression is due to reactive iron,” FASEB Journal, vol. 13, no. 13, pp. 1800–1809, 1999. View at Google Scholar · View at Scopus
  64. G. F. Vile and R. M. Tyrrell, “Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to a heme oxygenase-dependent increase in ferritin,” The Journal of Biological Chemistry, vol. 268, no. 20, pp. 14678–14681, 1993. View at Google Scholar · View at Scopus
  65. J. Z. He, J. J. D. Ho, S. Gingerich, D. W. Courtman, P. A. Marsden, and M. E. Ward, “Enhanced translation of heme oxygenase-2 preserves human endothelial cell viability during hypoxia,” The Journal of Biological Chemistry, vol. 285, no. 13, pp. 9452–9461, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  66. A. Yachie, Y. Niida, T. Wada et al., “Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency,” Journal of Clinical Investigation, vol. 103, no. 1, pp. 129–135, 1999. View at Google Scholar · View at Scopus
  67. K. D. Poss and S. Tonegawa, “Reduced stress defense in heme oxygenase 1-deficient cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 20, pp. 10925–10930, 1997. View at Publisher · View at Google Scholar · View at Scopus
  68. S. Doré, M. Takahashi, C. D. Ferris, L. D. Hester, D. Guastella, and S. H. Snyder, “Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 5, pp. 2445–2450, 1999. View at Publisher · View at Google Scholar · View at Scopus
  69. T. W. Wu, J. Wu, R. K. Li, D. Mickle, and D. Carey, “Albumin-bound bilirubins protect human ventricular myocytes against oxyradical damage,” Biochemistry and Cell Biology, vol. 69, no. 10-11, pp. 683–688, 1991. View at Google Scholar · View at Scopus
  70. R. Öllinger, H. Wang, K. Yamashita et al., “Therapeutic applications of bilirubin and biliverdin in transplantation,” Antioxidants and Redox Signaling, vol. 9, no. 12, pp. 2175–2185, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  71. R. Foresti, C. J. Green, and R. Motterlini, “Generation of bile pigments by haem oxygenase: a refined cellular strategy in response to stressful insults,” Biochemical Society Symposium, vol. 71, pp. 177–192, 2004. View at Google Scholar · View at Scopus
  72. P. A. Dennery, A. F. McDonagh, D. R. Spitz, and P. A. Rodgers, “Hyperbilirubinemia results in reduced oxidative injury in neonatal Gunn rats exposed to hyperoxia,” Free Radical Biology and Medicine, vol. 19, no. 4, pp. 395–404, 1995. View at Publisher · View at Google Scholar · View at Scopus
  73. H. A. Schwertner, W. G. Jackson, and G. Tolan, “Association of low serum concentration of bilirubin with increased risk of coronary artery disease,” Clinical Chemistry, vol. 40, no. 1, pp. 18–23, 1994. View at Google Scholar · View at Scopus
  74. L. H. Breimer, K. A. Spyropolous, A. F. Winder, D. P. Mikhailidis, and G. Hamilton, “Is bilirubin protective against coronary artery disease?” Clinical Chemistry, vol. 40, no. 10, pp. 1987–1988, 1994. View at Google Scholar · View at Scopus
  75. L. H. Breimer, G. Wannamethee, S. Ebrahim, and A. G. Shaper, “Serum bilirubin and risk of ischemic heart disease in middle-aged British men,” Clinical Chemistry, vol. 41, no. 10, pp. 1504–1508, 1995. View at Google Scholar · View at Scopus
  76. D. Erdogan, H. Gullu, E. Yildirim et al., “Low serum bilirubin levels are independently and inversely related to impaired flow-mediated vasodilation and increased carotid intima-media thickness in both men and women,” Atherosclerosis, vol. 184, no. 2, pp. 431–437, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  77. L. Vítek, M. Jirsa Jr., M. Brodanová et al., “Gilbert syndrome and ischemic heart disease: a protective effect of elevated bilirubin levels,” Atherosclerosis, vol. 160, no. 2, pp. 449–456, 2002. View at Publisher · View at Google Scholar
  78. A. C. Bulmer, J. T. Blanchfield, I. Toth, R. G. Fassett, and J. S. Coombes, “Improved resistance to serum oxidation in Gilbert's syndrome: a mechanism for cardiovascular protection,” Atherosclerosis, vol. 199, no. 2, pp. 390–396, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  79. J. F. Watchko, “Hyperbilirubinemia and bilirubin toxicity in the late preterm infant,” Clinics in Perinatology, vol. 33, no. 4, pp. 839–852, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  80. J. K. Sarady-Andrews, F. Liu, D. Gallo et al., “Biliverdin administration protects against endotoxin-induced acute lung injury in rats,” American Journal of Physiology, vol. 289, no. 6, pp. L1131–L1137, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  81. S. G. Tullius, M. Nieminen-Kelha, and U. Bachmann, “Induction of heme-oxygenase-1 prevents ischemia/reperfusion injury and improves long-term graft outcome in rat renal allografts,” Transplantation Proceedings, vol. 33, no. 1-2, pp. 1286–1287, 2001. View at Publisher · View at Google Scholar
  82. Y. Avihingsanon, N. Ma, E. Csizmadia et al., “Expression of protective genes in human renal allografts: a regulatory response to injury associated with graft rejection,” Transplantation, vol. 73, no. 7, pp. 1079–1085, 2002. View at Google Scholar · View at Scopus
  83. F. Amersi, R. Buelow, H. Kato et al., “Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury,” Journal of Clinical Investigation, vol. 104, no. 11, pp. 1631–1639, 1999. View at Google Scholar · View at Scopus
  84. S. W. Chung, X. Liu, A. A. Macias, R. M. Baron, and M. A. Perrella, “Heme oxygenase-1-derived carbon monoxide enhances the host defense response to microbial sepsis in mice,” Journal of Clinical Investigation, vol. 118, no. 1, pp. 239–247, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  85. R. Larsen, R. Gozzelino, V. Jeney et al., “A central role for free heme in the pathogenesis of severe sepsis,” Science Translational Medicine, vol. 2, no. 51, Article ID 51ra71, 2010. View at Publisher · View at Google Scholar · View at PubMed
  86. R. Takamiya, C. C. Hung, S. R. Hall et al., “High-mobility group box 1 contributes to lethality of endotoxemia in heme oxygenase-1-deficient mice,” American Journal of Respiratory Cell and Molecular Biology, vol. 41, no. 2, pp. 129–135, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  87. K. Tsoyi, Y. L. Tae, S. L. Young et al., “Heme-oxygenase-1 induction and carbon monoxide-releasing molecule inhibit lipopolysaccharide (LPS)-induced high-mobility group box 1 release in vitro and improve survival of mice in LPS- and cecal ligation and puncture-induced sepsis model in vivo,” Molecular Pharmacology, vol. 76, no. 1, pp. 173–182, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  88. J. K. Sarady, B. S. Zuckerbraun, M. Bilban et al., “Carbon monoxide protection against endotoxic shock involves reciprocal effects on iNOS in the lung and liver,” The FASEB Journal, vol. 18, no. 7, pp. 854–856, 2004. View at Google Scholar · View at Scopus
  89. S. Mazzola, M. Forni, M. Albertini et al., “Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs,” FASEB Journal, vol. 19, no. 14, pp. 2045–2047, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  90. L. A. Mitchell, M. M. Channell, C. M. Royer, S. W. Ryter, A. M. K. Choi, and J. D. McDonald, “Evaluation of inhaled carbon monoxide as an anti-inflammatory therapy in a nonhuman primate model of lung inflammation,” American Journal of Physiology, vol. 299, no. 6, pp. L891–L897, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  91. K. J. Davies, “Oxidative stress: the paradox of aerobic life,” Biochemical Society symposium, vol. 61, pp. 1–31, 1995. View at Google Scholar · View at Scopus
  92. R. M. Jackson, “Molecular, pharmacologic, and clinical aspects of oxygen-induced lung injury,” Clinics in Chest Medicine, vol. 11, no. 1, pp. 73–86, 1990. View at Google Scholar · View at Scopus
  93. P. J. Lee, J. Alam, S. L. Sylvester, N. Inamdar, L. Otterbein, and A. M. K. Choi, “Regulation of heme oxygenase-1 expression in vivo and in vitro in hyperoxic lung injury,” American Journal of Respiratory Cell and Molecular Biology, vol. 14, no. 6, pp. 556–568, 1996. View at Google Scholar · View at Scopus
  94. L. E. Otterbein, S. L. Otterbein, E. Ifedigbo et al., “MKK3 mitogen activated protein kinase pathway mediates carbon monoxide-induced protection against oxidant induced lung injury,” American Journal of Pathology, vol. 163, no. 6, pp. 2555–2563, 2003. View at Google Scholar · View at Scopus
  95. X. Zhang, P. Shan, G. Jiang et al., “Endothelial STAT3 is essential for the protective effects of HO-1 in oxidant-induced lung injury,” The FASEB Journal, vol. 20, no. 12, pp. 2156–2158, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  96. X. Wang, Y. Wang, H. P. Kim, K. Nakahira, S. W. Ryter, and A. M. K. Choi, “Carbon monoxide protects against hyperoxia-induced endothelial cell apoptosis by inhibiting reactive oxygen species formation,” The Journal of Biological Chemistry, vol. 282, no. 3, pp. 1718–1726, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  97. R. G. Brower, M. A. Matthay, A. Morris, D. Schoenfeld, B. T. Thompson, and A. Wheeler, “Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome,” The New England Journal of Medicine, vol. 342, no. 18, pp. 1301–1308, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  98. K. Tsushima, L. S. King, N. R. Aggarwal, A. De Gorordo, F. R. D'Alessio, and K. Kubo, “Acute lung injury review,” Internal Medicine, vol. 48, no. 9, pp. 621–630, 2009. View at Publisher · View at Google Scholar · View at Scopus
  99. A. S. Slutsky, “Lung injury caused by mechanical ventilation,” Chest, vol. 116, pp. 9S–15S, 1999. View at Publisher · View at Google Scholar · View at Scopus
  100. T. Dolinay, M. Szilasi, M. Liu, and A. M. K. Choi, “Inhaled carbon monoxide confers antiinflammatory effects against ventilator-induced lung injury,” American Journal of Respiratory and Critical Care Medicine, vol. 170, no. 6, pp. 613–620, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  101. A. Hoetzel, R. Schmidt, S. Vallbracht et al., “Carbon monoxide prevents ventilator-induced lung injury via caveolin-1,” Critical Care Medicine, vol. 37, no. 5, pp. 1708–1715, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  102. A. Hoetzel, T. Dolinay, S. Vallbracht et al., “Carbon monoxide protects against ventilator-induced lung injury via PPAR-γ and inhibition of Egr-1,” American Journal of Respiratory and Critical Care Medicine, vol. 177, no. 11, pp. 1223–1232, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  103. M. Bilban, F. H. Bach, S. L. Otterbein et al., “Carbon monoxide orchestrates a protective response through PPARγ,” Immunity, vol. 24, no. 5, pp. 601–610, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  104. M. Althaus, M. Fronius, Y. Buchäckert et al., “Carbon monoxide rapidly impairs alveolar fluid clearance by inhibiting epithelial sodium channels,” American Journal of Respiratory Cell and Molecular Biology, vol. 41, no. 6, pp. 639–650, 2009. View at Publisher · View at Google Scholar · View at PubMed
  105. X. Zhang, P. Shan, J. Alam, R. J. Davis, R. A. Flavell, and P. J. Lee, “Carbon monoxide modulates Fas/Fas ligand, caspases, and Bcl-2 family proteins via the p38α mitogen-activated protein kinase pathway during ischemia-reperfusion lung injury,” The Journal of Biological Chemistry, vol. 278, no. 24, pp. 22061–22070, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  106. X. Zhang, P. Shan, L. E. Otterbein et al., “Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3,” The Journal of Biological Chemistry, vol. 278, no. 2, pp. 1248–1258, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  107. X. Zhang, P. Shan, J. Alam, X. Y. Fu, and P. J. Lee, “Carbon monoxide differentially modulates STAT1 and STAT3 and inhibits apoptosis via a phosphatidylinositol 3-kinase/Akt and p38 kinase-dependent STAT3 pathway during anoxia-reoxygenation injury,” The Journal of Biological Chemistry, vol. 280, no. 10, pp. 8714–8721, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  108. T. Fujita, K. Toda, A. Karimova et al., “Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis,” Nature Medicine, vol. 7, no. 5, pp. 598–604, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  109. S. Mishra, T. Fujita, V. M. Lama et al., “Carbon monoxide rescues ischemic lungs by interrupting MAPK-driven expression of early growth response 1 gene and its downstream target genes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 13, pp. 5191–5196, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  110. R. Song, M. Kubo, D. Morse et al., “Carbon monoxide induces cytoprotection in rat orthotopic lung transplantation via anti-inflammatory and anti-apoptotic effects,” American Journal of Pathology, vol. 163, no. 1, pp. 231–242, 2003. View at Google Scholar · View at Scopus
  111. J. Kohmoto, A. Nakao, T. Kaizu et al., “Low-dose carbon monoxide inhalation prevents ischemia/reperfusion injury of transplanted rat lung grafts,” Surgery, vol. 140, no. 2, pp. 179–185, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  112. J. Kohmoto, A. Nakao, R. Sugimoto et al., “Carbon monoxide-saturated preservation solution protects lung grafts from ischemia-reperfusion injury,” Journal of Thoracic and Cardiovascular Surgery, vol. 136, no. 4, pp. 1067–1075, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  113. N. Hangai-Hoger, A. G. Tsai, P. Cabrales, M. Suematsu, and M. Intaglietta, “Microvascular and systemic effects following top load administration of saturated carbon monoxide-saline solution,” Critical Care Medicine, vol. 35, no. 4, pp. 1123–1132, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  114. S. F. Yet, M. A. Perrella, M. D. Layne et al., “Hypoxia induces severe right ventricular dilatation and infarction in heine oxygenase-1 null mice,” Journal of Clinical Investigation, vol. 103, no. 8, pp. R23–R29, 1999. View at Google Scholar · View at Scopus
  115. H. Zhou, H. Liu, S. L. Porvasnik et al., “Heme oxygenase-1 mediates the protective effects of rapamycin in monocrotaline-induced pulmonary hypertension,” Laboratory Investigation, vol. 86, no. 1, pp. 62–71, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  116. E. Dubuis, M. Potier, R. Wang, and C. Vandier, “Continuous inhalation of carbon monoxide attenuates hypoxic pulmonary hypertension development presumably through activation of BKCa channels,” Cardiovascular Research, vol. 65, no. 3, pp. 751–761, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  117. A. Kelekar, “Autophagy,” Annals of the New York Academy of Sciences, vol. 1066, pp. 259–271, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  118. C. He and D. J. Klionsky, “Regulation mechanisms and signaling pathways of autophagy,” Annual Review of Genetics, vol. 43, pp. 67–93, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  119. B. Levine and D. J. Klionsky, “Development by self-digestion: molecular mechanisms and biological functions of autophagy,” Developmental Cell, vol. 6, no. 4, pp. 463–477, 2004. View at Publisher · View at Google Scholar · View at Scopus
  120. N. Mizushima, B. Levine, A. M. Cuervo, and D. J. Klionsky, “Autophagy fights disease through cellular self-digestion,” Nature, vol. 451, no. 7182, pp. 1069–1075, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  121. D. J. Klionsky and S. D. Emr, “Autophagy as a regulated pathway of cellular degradation,” Science, vol. 290, no. 5497, pp. 1717–1721, 2000. View at Publisher · View at Google Scholar · View at Scopus
  122. T. Yorimitsu and D. J. Klionsky, “Autophagy: molecular machinery for self-eating,” Cell Death and Differentiation, vol. 12, no. 2, pp. 1542–1552, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  123. B. Levine, N. Mizushima, and H. W. Virgin, “Autophagy in immunity and inflammation,” Nature, vol. 469, no. 7330, pp. 323–335, 2011. View at Publisher · View at Google Scholar · View at PubMed
  124. B. Ravikumar, S. Sarkar, J. E. Davies et al., “Regulation of mammalian autophagy in physiology and pathophysiology,” Physiological Reviews, vol. 90, no. 4, pp. 1383–1435, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  125. Z. Yang and D. J. Klionsky, “Mammalian autophagy: core molecular machinery and signaling regulation,” Current Opinion in Cell Biology, vol. 22, no. 2, pp. 124–131, 2010. View at Publisher · View at Google Scholar · View at PubMed
  126. X. H. Liang, S. Jackson, M. Seaman et al., “Induction of autophagy and inhibition of tumorigenesis by beclin 1,” Nature, vol. 402, no. 6762, pp. 672–676, 1999. View at Publisher · View at Google Scholar · View at PubMed
  127. I. Tanida, T. Ueno, and E. Kominami, “LC3 conjugation system in mammalian autophagy,” International Journal of Biochemistry and Cell Biology, vol. 36, no. 12, pp. 2503–2518, 2004. View at Publisher · View at Google Scholar · View at PubMed
  128. D. R. Green, L. Galluzzi, and G. Kroemer, “Mitochondria and the autophagy-inflammation-cell death axis in organismal aging,” Science, vol. 333, no. 6046, pp. 1109–1112, 2011. View at Publisher · View at Google Scholar · View at PubMed
  129. B. Levine and J. Yuan, “Autophagy in cell death: an innocent convict?” Journal of Clinical Investigation, vol. 115, no. 10, pp. 2679–2688, 2005. View at Publisher · View at Google Scholar · View at PubMed
  130. Y. Tsujimoto and S. Shimizu, “Another way to die: autophagic programmed cell death,” Cell Death and Differentiation, vol. 12, no. 2, supplement, pp. 1528–1534, 2005. View at Publisher · View at Google Scholar · View at PubMed
  131. J. Debnath, K. R. Mills, N. L. Collins, M. J. Reginato, S. K. Muthuswamy, and J. S. Brugge, “The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini,” Cell, vol. 111, no. 1, pp. 29–40, 2002. View at Publisher · View at Google Scholar
  132. L. Jia, R. R. Dourmashkin, P. D. Allen, A. B. Gray, A. C. Newland, and S. M. Kelsey, “Inhibition of autophagy abrogates tumour necrosis factor α induced apoptosis in human T-lymphoblastic leukaemic cells,” British Journal of Haematology, vol. 98, no. 3, pp. 673–685, 1997. View at Google Scholar
  133. B. Inbal, S. Bialik, I. Sabanay, G. Shani, and A. Kimchi, “DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death,” Journal of Cell Biology, vol. 157, no. 3, pp. 455–468, 2002. View at Publisher · View at Google Scholar · View at PubMed
  134. F. Zhou, Y. Yang, and D. Xing, “Bcl-2 and Bcl-xL play important roles in the crosstalk between autophagy and apoptosis,” FEBS Journal, vol. 278, no. 3, pp. 403–413, 2011. View at Publisher · View at Google Scholar · View at PubMed
  135. V. M. Aita, X. H. Liang, V. V. V. S. Murty et al., “Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21,” Genomics, vol. 59, no. 1, pp. 59–65, 1999. View at Publisher · View at Google Scholar · View at PubMed
  136. S. Pattingre, A. Tassa, X. Qu et al., “Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy,” Cell, vol. 122, no. 6, pp. 927–939, 2005. View at Publisher · View at Google Scholar · View at PubMed
  137. S. Shimizu, T. Kanaseki, N. Mizushima et al., “Role of Bcl-2 family proteins in a non-apoptopic programmed cell death dependent on autophagy genes,” Nature Cell Biology, vol. 6, no. 12, pp. 1221–1228, 2004. View at Publisher · View at Google Scholar · View at PubMed
  138. Z. H. Chen, H. C. Lam, Y. Jin et al., “Autophagy protein microtubule-associated protein 1 light chain-3B (LC3B) activates extrinsic apoptosis during cigarette smoke-induced emphysema,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 44, pp. 18880–18885, 2010. View at Publisher · View at Google Scholar · View at PubMed
  139. H. P. Kim, X. Wang, Z. H. Chen et al., “Autophagic proteins regulate cigarette smoke-induced apoptosis:Protective role of heme oxygenase-1,” Autophagy, vol. 4, no. 7, pp. 887–895, 2008. View at Google Scholar
  140. D. J. Slebos, S. W. Ryter, M. van der Toorn et al., “Mitochondrial localization and function of heme oxygenase-1 in cigarette smoke-induced cell death,” American Journal of Respiratory Cell and Molecular Biology, vol. 36, no. 4, pp. 409–417, 2007. View at Publisher · View at Google Scholar · View at PubMed
  141. E. H. Carchman, J. Rao, P. A. Loughran, M. R. Rosengart, and B. S. Zuckerbraun, “Heme oxygenase-1-mediated autophagy protects against hepatocyte cell death and hepatic injury from infection/sepsis in mice,” Hepatology, vol. 53, no. 6, pp. 2053–2062, 2011. View at Publisher · View at Google Scholar · View at PubMed
  142. P. Waltz, E. H. Carchman, A. C. Young et al., “Lipopolysaccaride induces autophagic signaling in macrophages via a TLR4, heme oxygenase-1 dependent pathway,” Autophagy, vol. 7, no. 3, pp. 315–320, 2011. View at Publisher · View at Google Scholar · View at PubMed
  143. H. Zukor, W. Song, A. Liberman et al., “HO-1-mediated macroautophagy: a mechanism for unregulated iron deposition in aging and degenerating neural tissues,” Journal of Neurochemistry, vol. 109, no. 3, pp. 776–791, 2009. View at Publisher · View at Google Scholar · View at PubMed
  144. S. Bolisetty, A. M. Traylor, J. Kim et al., “Heme oxygenase-1 inhibits renal tubular macroautophagy in acute kidney injury,” Journal of the American Society of Nephrology, vol. 21, no. 10, pp. 1702–1712, 2010. View at Publisher · View at Google Scholar · View at PubMed
  145. S. J. Lee, S. W. Ryter, J. F. Xu et al., “Carbon monoxide activates autophagy via mitochondrial reactive oxygen species formation,” American Journal of Respiratory Cell and Molecular Biology, vol. 45, no. 4, pp. 867–873, 2011. View at Publisher · View at Google Scholar · View at PubMed
  146. R. Motterlini, B. E. Mann, and R. Foresti, “Therapeutic applications of carbon monoxide-releasing molecules,” Expert Opinion on Investigational Drugs, vol. 14, no. 11, pp. 1305–1318, 2005. View at Publisher · View at Google Scholar · View at PubMed
  147. R. Foresti, M. G. Bani-Hani, and R. Motterlini, “Use of carbon monoxide as a therapeutic agent: promises and challenges,” Intensive Care Medicine, vol. 34, no. 4, pp. 649–658, 2008. View at Publisher · View at Google Scholar · View at PubMed
  148. R. Motterlini, P. Sawle, J. Hammad et al., “CORM-A1: a new pharmacologically active carbon monoxide-releasing molecule,” FASEB Journal, vol. 19, no. 2, pp. 284–286, 2005. View at Publisher · View at Google Scholar · View at PubMed
  149. R. Foresti, J. Hammad, J. E. Clark et al., “Vasoactive properties of CORM-3, a novel water-soluble carbon monoxide-releasing molecule,” British Journal of Pharmacology, vol. 142, no. 3, pp. 453–460, 2004. View at Publisher · View at Google Scholar · View at PubMed
  150. R. Kretschmer, G. Gessner, H. Görls, S. H. Heinemann, and M. Westerhausen, “Dicarbonyl-bis(cysteamine)iron(II): a light induced carbon monoxide releasing molecule based on iron (CORM-S1),” Journal of Inorganic Biochemistry, vol. 105, no. 1, pp. 6–9, 2011. View at Publisher · View at Google Scholar · View at PubMed
  151. G. L. Bannenberg and H. L. A. Vieira, “Therapeutic applications of the gaseous mediators carbon monoxide and hydrogen sulfide,” Expert Opinion on Therapeutic Patents, vol. 19, no. 5, pp. 663–682, 2009. View at Publisher · View at Google Scholar · View at PubMed
  152. B. Sun, X. Zou, Y. Chen, P. Zhang, and G. Shi, “Preconditioning of carbon monoxide releasing molecule-derived CO attenuates LPS-induced activation of HUVEC,” International Journal of Biological Sciences, vol. 4, no. 5, pp. 270–278, 2008. View at Google Scholar
  153. U. Hasegawa, A. J. van der Vlies, E. Simeoni, C. Wandrey, and J. A. Hubbell, “Carbon monoxide-releasing micelles for immunotherapy,” Journal of the American Chemical Society, vol. 132, no. 51, pp. 18273–18280, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  154. B. Sun, H. Sun, C. Liu, J. Shen, Z. Chen, and X. Chen, “Role of CO-releasing molecules liberated CO in attenuating leukocytes sequestration and inflammatory responses in the lung of thermally injured mice,” Journal of Surgical Research, vol. 139, no. 1, pp. 128–135, 2007. View at Publisher · View at Google Scholar · View at PubMed
  155. G. Cepinskas, K. Katada, A. Bihari, and R. F. Potter, “Carbon monoxide liberated from carbon monoxide-releasing molecule CORM-2 attenuates inflammation in the liver of septic mice,” American Journal of Physiology, vol. 294, no. 1, pp. G184–G191, 2007. View at Publisher · View at Google Scholar · View at PubMed
  156. S. Mizuguchi, J. Stephen, R. Bihari et al., “CORM-3-derived CO modulates polymorphonuclear leukocyte migration across the vascular endothelium by reducing levels of cell surface-bound elastase,” American Journal of Physiology, vol. 297, no. 3, pp. H920–H929, 2009. View at Publisher · View at Google Scholar · View at PubMed
  157. R. Wang and L. Wu, “The chemical modification of K(Ca) channels by carbon monoxide in vascular smooth muscle cells,” The Journal of Biological Chemistry, vol. 272, no. 13, pp. 8222–8226, 1997. View at Publisher · View at Google Scholar
  158. A. M. Riesco-Fagundo, M. T. Pérez-García, C. González, and J. R. López-López, “O2 modulates large-conductance Ca2+-dependent K+ channels of rat chemoreceptor cells by a membrane-restricted and CO-sensitive mechanism,” Circulation Research, vol. 89, no. 5, pp. 430–436, 2001. View at Google Scholar
  159. S. E. J. Williams, P. Wootton, H. S. Mason et al., “Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel,” Science, vol. 306, no. 5704, pp. 2093–2097, 2004. View at Publisher · View at Google Scholar · View at PubMed
  160. S. E. Williams, S. P. Brazier, N. Baban et al., “A structural motif in the C-terminal tail of slo1 confers carbon monoxide sensitivity to human BKCa channels,” Pflugers Archiv, vol. 456, no. 3, pp. 561–572, 2008. View at Publisher · View at Google Scholar · View at PubMed
  161. J. H. Jaggar, A. Li, H. Parfenova et al., “Heme is a carbon monoxide receptor for large-conductance Ca 2+-activated K+ channels,” Circulation Research, vol. 97, no. 8, pp. 805–812, 2005. View at Publisher · View at Google Scholar · View at PubMed
  162. S. Hou, R. Xu, S. H. Heinemann, and T. Hoshi, “The RCK1 high-affinity Ca2+ sensor confers carbon monoxide sensitivity to Slo1 BK channels,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 10, pp. 4039–4043, 2008. View at Publisher · View at Google Scholar · View at PubMed
  163. V. Telezhkin, S. P. Brazier, R. Mears, C. T. Müller, D. Riccardi, and P. J. Kemp, “Cysteine residue 911 in C-terminal tail of human BKCaα channel subunit is crucial for its activation by carbon monoxide,” Pflugers Archiv European Journal of Physiology, vol. 461, no. 6, pp. 665–675, 2011. View at Publisher · View at Google Scholar · View at PubMed
  164. W. Wilkinson, H. C. Gadeberg, A. W. J. Harrison, N. D. Allen, D. Riccardi, and P. J. Kemp, “Carbon monoxide is a rapid modulator of recombinant and native P2X 2 ligand-gated ion channels,” British Journal of Pharmacology, vol. 158, no. 3, pp. 862–871, 2009. View at Publisher · View at Google Scholar · View at PubMed
  165. M. L. Dallas, J. L. Scragg, and C. Peers, “Modulation of hTREK-1 by carbon monoxide,” NeuroReport, vol. 19, no. 3, pp. 345–348, 2008. View at Publisher · View at Google Scholar · View at PubMed
  166. W. J. Wilkinson and P. J. Kemp, “The carbon monoxide donor, CORM-2, is an antagonist of ATP-gated, human P2X4 receptors,” Purinergic Signalling, vol. 7, no. 1, pp. 57–64, 2011. View at Publisher · View at Google Scholar · View at PubMed
  167. M. L. Dallas, J. P. Boyle, C. J. Milligan et al., “Carbon monoxide protects against oxidant-induced apoptosis via inhibition of Kv2.1,” FASEB Journal, vol. 25, no. 5, pp. 1519–1530, 2011. View at Publisher · View at Google Scholar · View at PubMed
  168. A. Rich, G. Farrugia, and J. L. Rae, “Carbon monoxide stimulates a potassium-selective current in rabbit corneal epithelial cells,” American Journal of Physiology, vol. 267, no. 2, pp. C435–C442, 1994. View at Google Scholar
  169. J. L. Scragg, M. L. Dallas, J. A. Wilkinson, G. Varadi, and C. Peers, “Carbon monoxide inhibits L-type Ca2+ channels via redox modulation of key cysteine residues by mitochondrial reactive oxygen species,” The Journal of Biological Chemistry, vol. 283, no. 36, pp. 24412–24419, 2008. View at Publisher · View at Google Scholar · View at PubMed
  170. W. J. Wilkinson and P. J. Kemp, “Carbon monoxide: an emerging regulator of ion channels,” Journal of Physiology, vol. 589, no. 13, pp. 3055–3062, 2011. View at Publisher · View at Google Scholar · View at PubMed
  171. I. Lim, S. J. Gibbons, G. L. Lyford et al., “Carbon monoxide activates human intestinal smooth muscle L-type Ca2+ channels through a nitric oxide-dependent mechanism,” American Journal of Physiology, vol. 288, no. 1, pp. G7–G14, 2005. View at Publisher · View at Google Scholar · View at PubMed
  172. I. M. Fearon, G. Varadi, S. Koch, I. Isaacsohn, S. G. Ball, and C. Peers, “Splice variants reveal the region involved in oxygen sensing by recombinant human L-type Ca2+ channels,” Circulation Research, vol. 87, no. 7, pp. 537–539, 2000. View at Google Scholar
  173. M. Desmard, J. Boczkowski, J. Poderoso, and R. Motterlini, “Mitochondrial and cellular heme-dependent proteins as targets for the bioactive function of the heme oxygenase/carbon monoxide system,” Antioxidants and Redox Signaling, vol. 9, no. 12, pp. 2139–2155, 2007. View at Publisher · View at Google Scholar · View at PubMed
  174. H. B. Suliman, M. S. Carraway, A. S. Ali, C. M. Reynolds, K. E. Welty-Wolf, and C. A. Piantadosi, “The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy,” Journal of Clinical Investigation, vol. 117, no. 12, pp. 3730–3741, 2007. View at Publisher · View at Google Scholar · View at PubMed
  175. S. Lancel, S. M. Hassoun, R. Favory, B. Decoster, R. Motterlini, and R. Neviere, “Carbon monoxide rescues mice from lethal sepsis by supporting mitochondrial energetic metabolism and activating mitochondrial biogenesis,” Journal of Pharmacology and Experimental Therapeutics, vol. 329, no. 2, pp. 641–648, 2009. View at Publisher · View at Google Scholar · View at PubMed
  176. L. Lo Iacono, J. Boczkowski, R. Zini et al., “A carbon monoxide-releasing molecule (CORM-3) uncouples mitochondrial respiration and modulates the production of reactive oxygen species,” Free Radical Biology and Medicine, vol. 50, no. 11, pp. 1556–1564, 2011. View at Publisher · View at Google Scholar · View at PubMed
  177. F. B. Mayr, A. Spiel, J. Leitner et al., “Effects of carbon monoxide inhalation during experimental endotoxemia in humans,” American Journal of Respiratory and Critical Care Medicine, vol. 171, no. 4, pp. 354–360, 2005. View at Publisher · View at Google Scholar · View at PubMed
  178. E. Bathoorn, D. J. Slebos, D. S. Postma et al., “Anti-inflammatory effects of inhaled carbon monoxide in patients with COPD: a pilot study,” European Respiratory Journal, vol. 30, no. 6, pp. 1131–1137, 2007. View at Publisher · View at Google Scholar · View at PubMed
  179. N. G. Abraham, A. Asija, G. Drummond, and S. Peterson, “Heme oxygenase -1 gene therapy: recent advances and therapeutic applications,” Current Gene Therapy, vol. 7, no. 2, pp. 89–108, 2007. View at Publisher · View at Google Scholar
  180. S. W. Ryter and A. M. K. Choi, “Heme oxygenase-1/carbon monoxide: from metabolism to molecular therapy,” American Journal of Respiratory Cell and Molecular Biology, vol. 41, no. 3, pp. 251–260, 2009. View at Publisher · View at Google Scholar · View at PubMed
  181. S. Ghosh, M. R. Wilson, S. Choudhury et al., “Effects of inhaled carbon monoxide on acute lung injury in mice,” American Journal of Physiology, vol. 288, no. 6, pp. L1003–L1009, 2005. View at Publisher · View at Google Scholar · View at PubMed
  182. C. E. Clayton, M. S. Carraway, H. B. Suliman et al., “Inhaled carbon monoxide and hyperoxic lung injury in rats,” American Journal of Physiology, vol. 281, no. 4, pp. L949–L957, 2001. View at Google Scholar