Hyperbaric oxygen induces apoptosis via a mitochondrial mechanism.
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.
Weber
Stefan U
SU
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
Koch
Andreas
A
Kankeleit
Jens
J
Schewe
Jens-Christian
JC
Siekmann
Ullrich
U
Stüber
Frank
F
Hoeft
Andreas
A
Schröder
Stefan
S
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
D019014:fas Receptor; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D010100:Oxygen