Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia.

Abstract

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.

• Authors: Carsten Lundby, Henriette Pilegaard, Gerrit van Hall, Mikael Sander, Jose Calbet, Steffen Loft, Peter Møller
• Journal: Toxicology (Toxicology) Vol. 192 Issue 2-3 Pg. 229-36 (Nov 05 2003) ISSN: 0300-483X [Print] Ireland
• PMID: 14580789 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adaptation, Physiological (physiology)
• Adult
• Altitude Sickness (physiopathology)
• DNA Damage
• DNA Repair
• Female
• Humans
• Male
• Muscle, Skeletal (metabolism, physiopathology)
• Oxidative Stress (physiology)
• Time Factors