title: High altitude exposure alters gene expression levels of DNA repair enzymes, and modulates fatty acid metabolism by SIRT4 induction in human skeletal muscle.
abstract: We hypothesized that high altitude exposure and physical activity associated with the attack to Mt Everest could alter mRNA levels of DNA repair and metabolic enzymes and cause oxidative stress-related challenges in human skeletal muscle. Therefore, we have tested eight male mountaineers (25-40 years old) before and after five weeks of exposure to high altitude, which included attacks to peaks above 8000m. Data gained from biopsy samples from vastus lateralis revealed increased mRNA levels of both cytosolic and mitochondrial superoxide dismutase. On the other hand 8-oxoguanine DNA glycosylase (OGG1) mRNA levels tended to decrease while Ku70 mRNA levels and SIRT6 decreased with altitude exposure. The levels of SIRT1 and SIRT3 mRNA did not change significantly. However, SIRT4 mRNA level increased significantly, which could indicate decreases in fatty acid metabolism, since SIRT4 is one of the important regulators of this process. Within the limitations of this human study, data suggest that combined effects of high altitude exposure and physical activity climbing to Mt. Everest, could jeopardize the integrity of the particular chromosome.
authors.affiliation: Research Institute of Sport Science, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Acs
authors.affiliation: Research Institute of Sport Science, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Bori
authors.affiliation: Research Institute of Sport Science, Semmelweis University, Budapest, Hungary.
authors.forename: Masaki
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Research Institute of Sport Science, Semmelweis University, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Osvath
authors.affiliation: Research Institute of Sport Science, Semmelweis University, Budapest, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Berkes
authors.affiliation: School of Kinesiology, Faculty of Health Sciences, University of Western Ontario, London, Canada; Department of Physiology, Faculty of Medicine and Dentistry, University of Western Ontario, London, Canada.
authors.forename: Albert W
authors.initials: AW
authors.lastname: Taylor
authors.affiliation: Research Institute, Bejing Sport University, Beijing, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Yang
authors.affiliation: Research Institute of Sport Science, Semmelweis University, Budapest, Hungary. Electronic address: radak@tf.hu.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Radak
mesh_terms: D000328:Adult; D000531:Altitude; D034961:Antigens, Nuclear / Q000378:metabolism; D045647:DNA Glycosylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009051:Mountaineering / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism; D056566:Sirtuin 3 / Q000378:metabolism; D037761:Sirtuins / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C447939:SIRT1 protein, human; C466093:SIRT3 protein, human; C525357:SIRT4 protein, human; C516592:SIRT6 protein, human; D056564:Sirtuin 1; D056566:Sirtuin 3; D037761:Sirtuins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D045643:DNA Repair Enzymes
keywords: DNA damage; High altitude; Oxidative stress; Sirtuins