title: Hyperbaric oxygen induces apoptosis via a mitochondrial mechanism.
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.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of Bonn Medical Center, Sigmund Freud Str. 25, 53105 Bonn, Germany. Stefan.weber@ukb.uni-bonn.de
authors.forename: Stefan U
authors.initials: SU
authors.lastname: Weber
authors.forename: Andreas
authors.initials: A
authors.lastname: Koch
authors.forename: Jens
authors.initials: J
authors.lastname: Kankeleit
authors.forename: Jens-Christian
authors.initials: JC
authors.lastname: Schewe
authors.forename: Ullrich
authors.initials: U
authors.lastname: Siekmann
authors.forename: Frank
authors.initials: F
authors.lastname: Stüber
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeft
authors.forename: Stefan
authors.initials: S
authors.lastname: Schröder
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D053938:DNA Fragmentation; D006801:Humans; D006931:Hyperbaric Oxygenation; D019169:Jurkat Cells; D008214:Lymphocytes / Q000378:metabolism; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism*; D018805:Sepsis; D019014:fas Receptor / Q000378:metabolism
chemical_list: D019014:fas Receptor; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D010100:Oxygen