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Hyperbaric oxygen induces apoptosis via a mitochondrial mechanism

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Abstract

During therapeutic hyperbaric oxygenation lymphocytes are exposed to high partial pressures of oxygen. This study aimed to analyze the mechanism of apoptosis induction by hyperbaric oxygen. For intervals of 0.5–4 h Jurkat-T-cells were exposed to ambient air or oxygen atmospheres at 1–3 absolute atmospheres. Apoptosis was analyzed by phosphatidylserine externalization, caspase-3 activation and DNA-fragmentation using flow cytometry. Apoptosis was already induced after 30 min of hyperbaric oxygenation (HBO, P < 0.05). The death receptor Fas was downregulated. Inhibition of caspase-9 but not caspase-8 blocked apoptosis induction by HBO. Hyperbaric oxygen caused a loss of mitochondrial membrane potential and caspase-9 induction. The mitochondrial pro-survival protein Bcl-2 was upregulated, and antagonizing Bcl-2 function potentiated apoptosis induction by HBO. In conclusion, a single exposure to hyperbaric oxygenation induces lymphocyte apoptosis by a mitochondrial and not a Fas-related mechanism. Regulation of Fas and Bcl-2 may be regarded as protective measures of the cell in response to hyperbaric oxygen.

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References

  1. Tibbles PM, Edelsberg JS (1996) Hyperbaric-oxygen therapy. N Engl J Med 334:1642–1648. doi:10.1056/NEJM199606203342506

    Article  PubMed  CAS  Google Scholar 

  2. Frey G, Lampl L, Radermacher P, Bock KH (1998) Hyperbaric oxygenation. An area for the anesthetist? Anaesthesist 47:269–289. doi:10.1007/s001010050558

    Article  PubMed  CAS  Google Scholar 

  3. Muth CM, Shank ES (2000) Gas embolism. N Engl J Med 342:476–482. doi:10.1056/NEJM200002173420706

    Article  PubMed  CAS  Google Scholar 

  4. Leach RM, Rees PJ, Wilmshurst P (1998) Hyperbaric oxygen therapy. BMJ 317:1140–1143

    PubMed  CAS  Google Scholar 

  5. Enoch S, Grey JE, Harding KG (2006) ABC of wound healing. Non-surgical and drug treatments. BMJ 332:900–903. doi:10.1136/bmj.332.7546.900

    Article  PubMed  Google Scholar 

  6. Gill AL, Bell CN (2004) Hyperbaric oxygen: its uses, mechanisms of action and outcomes. QJM 97:385–395. doi:10.1093/qjmed/hch074

    Article  PubMed  CAS  Google Scholar 

  7. Buras JA, Holt D, Orlow D, Belikoff B, Pavlides S, Reenstra WR (2006) Hyperbaric oxygen protects from sepsis mortality via an interleukin-10-dependent mechanism. Crit Care Med 34:2624–2629. doi:10.1097/01.CCM.0000239438.22758.E0

    Article  PubMed  CAS  Google Scholar 

  8. Calzia E, Oter S, Muth CM, Radermacher P (2006) Evolving career of hyperbaric oxygen in sepsis: from augmentation of oxygen delivery to the modulation of the immune response. Crit Care Med 34:2693–2695. doi:10.1097/01.CCM.0000240782.44414.3A

    Article  PubMed  Google Scholar 

  9. Oter S, Radermacher P, Matejovic M (2006) Can (hyperbaric) oxygen turn off the motor of multiorgan dysfunction? Intensive Care Med 32:1694–1696. doi:10.1007/s00134-006-0379-z

    Article  PubMed  Google Scholar 

  10. Muth CM, Radermacher P, Cuzzocrea S (2005) Hyperbaric oxygen and sepsis: time to recognize. Intensive Care Med 31:1150–1152. doi:10.1007/s00134-005-2700-7

    Article  PubMed  Google Scholar 

  11. Treacher DF, Leach RM (1998) Oxygen transport-1. Basic principles. BMJ 317:1302–1306

    PubMed  CAS  Google Scholar 

  12. Granowitz EV, Skulsky EJ, Benson RM et al (2002) Exposure to increased pressure or hyperbaric oxygen suppresses interferon-gamma secretion in whole blood cultures of healthy humans. Undersea Hyperb Med 29:216–225

    PubMed  CAS  Google Scholar 

  13. Benson RM, Minter LM, Osborne BA, Granowitz EV (2003) Hyperbaric oxygen inhibits stimulus-induced proinflammatory cytokine synthesis by human blood-derived monocyte-macrophages. Clin Exp Immunol 134:57–62. doi:10.1046/j.1365-2249.2003.02248.x

    Article  PubMed  CAS  Google Scholar 

  14. Bitterman N, Bitterman H, Kinarty A, Melamed Y, Lahat N (1993) Effect of a single exposure to hyperbaric oxygen on blood mononuclear cells in human subjects. Undersea Hyperb Med 20:197–204

    PubMed  CAS  Google Scholar 

  15. Bitterman N, Lahat N, Rosenwald T, Kinarty A, Melamed Y, Bitterman H (1994) Effect of hyperbaric oxygen on tissue distribution of mononuclear cell subsets in the rat. J Appl Physiol 77:2355–2359

    PubMed  CAS  Google Scholar 

  16. Groger M, Speit G, Radermacher P, Muth CM (2005) Interaction of hyperbaric oxygen, nitric oxide, and heme oxygenase on DNA strand breaks in vivo. Mutat Res 572:167–172. doi:10.1016/j.mrfmmm.2005.01.015

    PubMed  Google Scholar 

  17. Speit G, Dennog C, Radermacher P, Rothfuss A (2002) Genotoxicity of hyperbaric oxygen. Mutat Res 512:111–119. doi:10.1016/S1383-5742(02)00045-5

    Article  PubMed  CAS  Google Scholar 

  18. Rothfuss A, Radermacher P, Speit G (2001) Involvement of heme oxygenase-1 (HO-1) in the adaptive protection of human lymphocytes after hyperbaric oxygen (HBO) treatment. Carcinogenesis 22:1979–1985. doi:10.1093/carcin/22.12.1979

    Article  PubMed  CAS  Google Scholar 

  19. Muth CM, Glenz Y, Klaus M, Radermacher P, Speit G, Leverve X (2004) Influence of an orally effective SOD on hyperbaric oxygen-related cell damage. Free Radic Res 38:927–932. doi:10.1080/10715760412331273197

    Article  PubMed  CAS  Google Scholar 

  20. Speit G, Dennog C, Eichhorn U, Rothfuss A, Kaina B (2000) Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. Carcinogenesis 21:1795–1799. doi:10.1093/carcin/21.10.1795

    Article  PubMed  CAS  Google Scholar 

  21. Gadd MA, McClellan DS, Neuman TS, Hansbrough JF (1990) Effect of hyperbaric oxygen on murine neutrophil and T-lymphocyte functions. Crit Care Med 18:974–979. doi:10.1097/00003246-199009000-00014

    Article  PubMed  CAS  Google Scholar 

  22. Granowitz EV, Tonomura N, Benson RM et al (2005) Hyperbaric oxygen inhibits benign and malignant human mammary epithelial cell proliferation. Anticancer Res 25:3833–3842

    PubMed  CAS  Google Scholar 

  23. Won WD, Ross HC, Deig EF (1976) Influence of cold or hyperbaric helium-oxygen environments on mouse response to a respiratory viral infection. Aviat Space Environ Med 47:704–707

    PubMed  CAS  Google Scholar 

  24. Won WD, Ross HC (1975) Catecholamine and phagocytic responses in infected mice exposed to hyperbaric helium-oxygen atmospheres. Aviat Space Environ Med 46:191–193

    PubMed  CAS  Google Scholar 

  25. Jacobs BB, Thuning CA, Sacksteder MR, Warren J (1979) Extended skin allograft survival in mice during prolonged exposure to hyperbaric oxygen. Transplantation 28:70–72. doi:10.1097/00007890-197907000-00017

    Article  PubMed  CAS  Google Scholar 

  26. Erdmann D, Roth AC, Hussmann J et al (1995) Skin allograft rejection and hyperbaric oxygen treatment in immune-histoincompatible mice. Undersea Hyperb Med 22:395–399

    PubMed  CAS  Google Scholar 

  27. Erdmann D, Roth AC, Hussmann J et al (1996) Hyperbaric oxygen and cyclosporine as a combined treatment regimen to prevent skin allograft rejection in immunohistoincompatible mice. Ann Plast Surg 36:304–308. doi:10.1097/00000637-199603000-00013

    Article  PubMed  CAS  Google Scholar 

  28. Yin D, Zhou C, Kusaka I et al (2003) Inhibition of apoptosis by hyperbaric oxygen in a rat focal cerebral ischemic model. J Cereb Blood Flow Metab 23:855–864. doi:10.1097/01.WCB.0000073946.29308.55

    Article  PubMed  CAS  Google Scholar 

  29. Ostrowski RP, Colohan AR, Zhang JH (2005) Mechanisms of hyperbaric oxygen-induced neuroprotection in a rat model of subarachnoid hemorrhage. J Cereb Blood Flow Metab 25:554–571. doi:10.1038/sj.jcbfm.9600048

    Article  PubMed  CAS  Google Scholar 

  30. Zhang Q, Chang Q, Cox RA, Gong X, Gould LJ (2008) Hyperbaric Oxygen attenuates apoptosis and decreases inflammation in an ischemic wound model. J Invest Dermatol 128(8):2102–2112

    PubMed  CAS  Google Scholar 

  31. Conconi MT, Baiguera S, Guidolin D et al (2003) Effects of hyperbaric oxygen on proliferative and apoptotic activities and reactive oxygen species generation in mouse fibroblast 3T3/J2 cell line. J Investig Med 51:227–232. doi:10.2310/6650.2003.39201

    Article  PubMed  CAS  Google Scholar 

  32. Ganguly BJ, Tonomura N, Benson RM, Osborne BA, Granowitz EV (2002) Hyperbaric oxygen enhances apoptosis in hematopoietic cells. Apoptosis 7:499–510. doi:10.1023/A:1020686908831

    Article  PubMed  CAS  Google Scholar 

  33. Chen YC, Chen SY, Ho PS et al (2007) Apoptosis of T-leukemia and B-myeloma cancer cells induced by hyperbaric oxygen increased phosphorylation of p38 MAPK. Leuk Res 31:805–815. doi:10.1016/j.leukres.2006.09.016

    Article  PubMed  CAS  Google Scholar 

  34. Green DR, Ferguson TA (2001) The role of Fas ligand in immune privilege. Nat Rev Mol Cell Biol 2:917–924. doi:10.1038/35103104

    Article  PubMed  CAS  Google Scholar 

  35. Krammer PH (2000) CD95’s deadly mission in the immune system. Nature 407:789–795. doi:10.1038/35037728

    Article  PubMed  CAS  Google Scholar 

  36. Wajant H (2002) The Fas signaling pathway: more than a paradigm. Science 296:1635–1636. doi:10.1126/science.1071553

    Article  PubMed  CAS  Google Scholar 

  37. Zamzami N, Kroemer G (2001) The mitochondrion in apoptosis: how Pandora’s box opens. Nat Rev Mol Cell Biol 2:67–71. doi:10.1038/35048073

    Article  PubMed  CAS  Google Scholar 

  38. Martinou JC, Green DR (2001) Breaking the mitochondrial barrier. Nat Rev Mol Cell Biol 2:63–67. doi:10.1038/35048069

    Article  PubMed  CAS  Google Scholar 

  39. Willis SN, Adams JM (2005) Life in the balance: how BH3-only proteins induce apoptosis. Curr Opin Cell Biol 17:617–625. doi:10.1016/j.ceb.2005.10.001

    Article  PubMed  CAS  Google Scholar 

  40. Rasola A, Bernardi P (2007) The mitochondrial permeability transition pore and its involvement in cell death and in disease pathogenesis. Apoptosis 12:815–833. doi:10.1007/s10495-007-0723-y

    Article  PubMed  CAS  Google Scholar 

  41. Kim HE, Du F, Fang M, Wang X (2005) Formation of apoptosome is initiated by cytochrome c-induced dATP hydrolysis and subsequent nucleotide exchange on Apaf-1. Proc Natl Acad Sci USA 102:17545–17550. doi:10.1073/pnas.0507900102

    Article  PubMed  CAS  Google Scholar 

  42. Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770–776. doi:10.1038/35037710

    Article  PubMed  CAS  Google Scholar 

  43. Nicholson DW, Ali A, Thornberry NA et al (1995) Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376:37–43. doi:10.1038/376037a0

    Article  PubMed  CAS  Google Scholar 

  44. Schneider U, Schwenk HU, Bornkamm G (1977) Characterization of EBV-genome negative “null” and “T” cell lines derived from children with acute lymphoblastic leukemia and leukemic transformed non-Hodgkin lymphoma. Int J Cancer 19:621–626. doi:10.1002/ijc.2910190505

    Article  PubMed  CAS  Google Scholar 

  45. Martin DA, Siegel RM, Zheng L, Lenardo MJ (1998) Membrane oligomerization and cleavage activates the caspase-8 (FLICE/MACHalpha1) death signal. J Biol Chem 273:4345–4349. doi:10.1074/jbc.273.8.4345

    Article  PubMed  CAS  Google Scholar 

  46. Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316. doi:10.1126/science.281.5381.1312

    Article  PubMed  CAS  Google Scholar 

  47. Milanesi E, Costantini P, Gambalunga A et al (2006) The mitochondrial effects of small organic ligands of BCL-2: sensitization of BCL-2-overexpressing cells to apoptosis by a pyrimidine-2, 4, 6-trione derivative. J Biol Chem 281:10066–10072. doi:10.1074/jbc.M513708200

    Article  PubMed  CAS  Google Scholar 

  48. Ettorre A, Andreassi M, Anselmi C, Neri P, Andreassi L, Di Stefano A (2003) Involvement of oxidative stress in apoptosis induced by a mixture of isothiazolinones in normal human keratinocytes. J Invest Dermatol 121:328–336. doi:10.1046/j.1523-1747.2003.12360.x

    Article  PubMed  CAS  Google Scholar 

  49. Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C (1991) A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods 139:271–279. doi:10.1016/0022-1759(91)90198-O

    Article  PubMed  CAS  Google Scholar 

  50. Smiley ST, Reers M, Mottola-Hartshorn C et al (1991) Intracellular heterogeneity in mitochondrial membrane potentials revealed by a J-aggregate-forming lipophilic cation JC-1. Proc Natl Acad Sci USA 88:3671–3675. doi:10.1073/pnas.88.9.3671

    Article  PubMed  CAS  Google Scholar 

  51. Reers M, Smiley ST, Mottola-Hartshorn C, Chen A, Lin M, Chen LB (1995) Mitochondrial membrane potential monitored by JC-1 dye. Methods Enzymol 260:406–417. doi:10.1016/0076-6879(95)60154-6

    Article  PubMed  CAS  Google Scholar 

  52. Cossarizza A, Baccarani-Contri M, Kalashnikova G, Franceschi C (1993) A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5, 5′, 6, 6′-tetrachloro-1, 1′, 3, 3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochem Biophys Res Commun 197:40–45. doi:10.1006/bbrc.1993.2438

    Article  PubMed  CAS  Google Scholar 

  53. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310. doi:10.1097/00003246-200107000-00002

    Article  PubMed  CAS  Google Scholar 

  54. Brun-Buisson C (2000) The epidemiology of the systemic inflammatory response. Intensive Care Med 26(Suppl 1):S64–S74. doi:10.1007/s001340051121

    Article  PubMed  Google Scholar 

  55. Brunkhorst FM (2006) Epidemiology, economy and practice—results of the German study on prevalence by the competence network sepsis (SepNet) [Epidemiologie, Okonomie und Praxis—Ergebnisse der deutschen Pravalenzstudie des Kompetenznetzwerkes Sepsis (SepNet)]. Anasthesiol Intensivmed Notfallmed Schmerzther 41(1):43–44

  56. Hotchkiss RS, Chang KC, Swanson PE et al (2000) Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte. Nat Immunol 1:496–501. doi:10.1038/82741

    Article  PubMed  CAS  Google Scholar 

  57. Hotchkiss RS, Karl IE (2003) The pathophysiology and treatment of sepsis. N Engl J Med 348:138–150. doi:10.1056/NEJMra021333

    Article  PubMed  CAS  Google Scholar 

  58. Perl M, Chung CS, Ayala A (2005) Apoptosis. Crit Care Med 33:S526–S529. doi:10.1097/01.CCM.0000185499.28006.4C

    Article  PubMed  Google Scholar 

  59. Salmena L, Lemmers B, Hakem A et al (2003) Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. Genes Dev 17(7):883–895 Epub 2003 Mar 21

    Article  PubMed  CAS  Google Scholar 

  60. Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305:626–629. doi:10.1126/science.1099320

    Article  PubMed  CAS  Google Scholar 

  61. Green DR, Kroemer G (2005) Pharmacological manipulation of cell death: clinical applications in sight? J Clin Invest 115:2610–2617. doi:10.1172/JCI26321

    Article  PubMed  CAS  Google Scholar 

  62. Hotchkiss RS, Osmon SB, Chang KC, Wagner TH, Coopersmith CM, Karl IE (2005) Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochondrial pathways. J Immunol 174:5110–5118

    PubMed  CAS  Google Scholar 

  63. Wada K, Miyazawa T, Nomura N et al (2000) Mn-SOD and Bcl-2 expression after repeated hyperbaric oxygenation. Acta Neurochir Suppl (Wien) 76:285–290

    CAS  Google Scholar 

  64. Tonomura N, Granowitz EV (2007) Hyperbaric oxygen: a potential new therapy for leukemia? Leuk Res 31:745–746. doi:10.1016/j.leukres.2006.11.020

    Article  PubMed  CAS  Google Scholar 

  65. Halliwell B (2003) Oxidative stress in cell culture: an under-appreciated problem? FEBS Lett 540:3–6. doi:10.1016/S0014-5793(03)00235-7

    Article  PubMed  CAS  Google Scholar 

  66. Halliwell B, Cross CE (1994) Oxygen-derived species: their relation to human disease and environmental stress. Environ Health Perspect 102(Suppl 10):5–12. doi:10.2307/3432205

    Article  PubMed  CAS  Google Scholar 

  67. Cross CE, Valacchi G, Schock B et al (2002) Environmental oxidant pollutant effects on biologic systems: a focus on micronutrient antioxidant-oxidant interactions. Am J Respir Crit Care Med 166:S44–S50. doi:10.1164/rccm.2206015

    Article  PubMed  Google Scholar 

  68. Vissers MC, Wilkie RP (2007) Ascorbate deficiency results in impaired neutrophil apoptosis and clearance and is associated with up-regulation of hypoxia-inducible factor 1alpha. J Leukoc Biol 81:1236–1244. doi:10.1189/jlb.0806541

    Article  PubMed  CAS  Google Scholar 

  69. Weinmann M, Marini P, Jendrossek V et al (2004) Influence of hypoxia on TRAIL-induced apoptosis in tumor cells. Int J Radiat Oncol Biol Phys 58:386–396. doi:10.1016/j.ijrobp.2003.09.052

    PubMed  CAS  Google Scholar 

  70. Bader N, Bosy-Westphal A, Koch A et al (2007) Effect of hyperbaric oxygen and vitamin C and E supplementation on biomarkers of oxidative stress in healthy men. Br J Nutr 98:826–833. doi:10.1017/S0007114507744380

    Article  PubMed  CAS  Google Scholar 

  71. Ferrer MD, Sureda A, Batle JM, Tauler P, Tur JA, Pons A (2007) Scuba diving enhances endogenous antioxidant defenses in lymphocytes and neutrophils. Free Radic Res 41:274–281. doi:10.1080/10715760601080371

    Article  PubMed  CAS  Google Scholar 

  72. Benedetti S, Lamorgese A, Piersantelli M, Pagliarani S, Benvenuti F, Canestrari F (2004) Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. Clin Biochem 37:312–317. doi:10.1016/j.clinbiochem.2003.12.001

    Article  PubMed  CAS  Google Scholar 

  73. Ott M, Gogvadze V, Orrenius S, Zhivotovsky B (2007) Mitochondria, oxidative stress and cell death. Apoptosis 12:913–922. doi:10.1007/s10495-007-0756-2

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Caroline von dem Bussche, Makbule Kobilay and Marcel Schiff for excellent technical assistance. This study was supported by a grant from the German Department of Defense.

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Authors and Affiliations

  1. Department of Anesthesiology and Intensive Care Medicine, University of Bonn Medical Center, Sigmund Freud Str. 25, 53105, Bonn, Germany

    Stefan U. Weber, Jens Kankeleit, Jens-Christian Schewe & Andreas Hoeft

  2. German Naval Medical Institute, Kopperpahler Allee 120, 24119, Kronshagen, Germany

    Andreas Koch

  3. Department of Anesthesiology and Intensive Care Medicine, University Hospital of Aachen, Pauwelsstraße 30, 52057, Aachen, Germany

    Ullrich Siekmann

  4. Department of Anaesthesiology and Pain Therapy, University Hospital Bern “Inselspital”, 3010, Bern, Switzerland

    Frank Stüber

  5. Clinic of Anesthesiology and Intensive Care Medicine, Westküstenklinikum Heide, Esmarch Str. 50, 25746, Heide, Germany

    Stefan Schröder

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  1. Stefan U. Weber
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Weber, S.U., Koch, A., Kankeleit, J. et al. Hyperbaric oxygen induces apoptosis via a mitochondrial mechanism. Apoptosis 14, 97–107 (2009). https://doi.org/10.1007/s10495-008-0280-z

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