Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia.
Recent research suggests that high-altitude hypoxia may serve as a model for prolonged oxidative stress in healthy humans. In this study, we investigated the consequences of prolonged high-altitude hypoxia on the basal level of oxidative damage to nuclear DNA in muscle cells, a major oxygen-consuming tissue. Muscle biopsies from seven healthy humans were obtained at sea level and after 2 and 8 weeks of hypoxia at 4100 m.a.s.l. We found increased levels of strand breaks and endonuclease III-sensitive sites after 2 weeks of hypoxia, whereas oxidative DNA damage detected by formamidopyrimidine DNA glycosylase (FPG) protein was unaltered. The expression of 8-oxoguanine DNA glycosylase 1 (OGG1), determined by quantitative RT-PCR of mRNA levels did not significantly change during high-altitude hypoxia, although the data could not exclude a minor upregulation. The expression of heme oxygenase-1 (HO-1) was unaltered by prolonged hypoxia, in accordance with the notion that HO-1 is an acute stress response protein. In conclusion, our data indicate high-altitude hypoxia may serve as a good model for oxidative stress and that antioxidant genes are not upregulated in muscle tissue by prolonged hypoxia despite increased generation of oxidative DNA damage.
Lundby
Carsten
C
The Copenhagen Muscle Research Centre, Rigshospitalet, DK-2200 Copenhagen N, Denmark.
Pilegaard
Henriette
H
van Hall
Gerrit
G
Sander
Mikael
M
Calbet
Jose
J
Loft
Steffen
S
Møller
Peter
P
D000222:Adaptation, Physiological / Q000502:physiology; D000328:Adult; D000532:Altitude Sickness / Q000503:physiopathology*; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress / Q000502:physiology*; D013997:Time Factors