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.
The Copenhagen Muscle Research Centre, Rigshospitalet, DK-2200 Copenhagen N, Denmark.
Carsten
C
Lundby
Henriette
H
Pilegaard
Gerrit
G
van Hall
Mikael
M
Sander
Jose
J
Calbet
Steffen
S
Loft
Peter
P
Møller
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