Macrophages that survive hyperoxia exposure have higher superoxide dismutase activities in their mitochondria.
Prolonged exposure to hyperoxia, which is routinely used in patients with severe respiratory failure, leads to the generation of excessive reactive oxygen species, resulting in lung injury. In the present study, we focused on macrophages and their survival, superoxide dismutase (SOD) activity in mitochondria (Mn-SOD activity), and mitochondrial DNA (mtDNA) mutation after exposure to hyperoxia. Macrophages were cultured under two different conditions: normoxia and intermittent hyperoxia. The number of cells exposed to intermittent hyperoxia for 3 weeks significantly decreased, compared with the number of cells exposed to normoxia. The Mn-SOD activity of the cells that survived intermittent hyperoxia exposure was significantly higher than that of the cells exposed to normoxia. Direct sequencing and a PCR-RFLP assay did not provide any evidence of mutation in the cells that survived intermittent hyperoxia exposure. In conclusion, an increase in the antioxidative activity of mitochondria is important for the survival of macrophages exposed to hyperoxia, and the increased activity level possibly enhances protective effects against mtDNA mutations in surviving cells.
Kokubo
Kenichi
K
Department of Medical Engineering and Technology, School of Allied Health Sciences, Kitasato University, Kanagawa 228-8555, Japan. kokubo@kitasato-u.ac.jp
Soeda
Saki
S
Shinbo
Toshihiro
T
Hirose
Minoru
M
Fuku
Noriyuki
N
Nishigaki
Yutaka
Y
Tanaka
Masashi
M
Kobayashi
Hirosuke
H
D001483:Base Sequence; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics; D006801:Humans; D018496:Hyperoxia / Q000201:enzymology* / Q000473:pathology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology*; D008969:Molecular Sequence Data; D010100:Oxygen / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013482:Superoxide Dismutase / Q000378:metabolism
D004272:DNA, Mitochondrial; D013482:Superoxide Dismutase; D010100:Oxygen