Acute and severe hypobaric hypoxia increases oxidative stress and impairs mitochondrial function in mouse skeletal muscle

• Published in: Journal of applied physiology (1985) Vol. 99; no. 4; pp. 1247 - 1253
• Main Authors: Magalhaes, Jose, Ascensao, Antonio, Soares, Jose M. C, Ferreira, Rita, Neuparth, Maria J, Marques, Franklim, Duarte, Jose A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.10.2005; American Physiological Society
• Subjects: Acute Disease; Animals; Atmospheric Pressure; Biological and medical sciences; Carbonyl compounds; Fundamental and applied biological sciences. Psychology; Hypoxia; Hypoxia - etiology; Hypoxia - metabolism; Hypoxia - physiopathology; In Vitro Techniques; Male; Mice; Mice, Inbred Strains; Mitochondria, Muscle - metabolism; Mitochondrial DNA; Muscle, Skeletal - metabolism; Muscular system; Oxidation; Oxidative Stress; Oxygen Consumption - drug effects; Respiration; Respiratory function; Rodents; Severity of Illness Index; Superoxides - metabolism; Vitamin E - metabolism; Vitamin E - pharmacology; High altitude; Oxidative stress; Oxygen; antioxidants; Acute; Rodentia; vitamin E; Environmental factor; oxidative damage; E-Vitamins; Antioxidant; Striated muscle; Vertebrata; Mitochondria; Mammalia; Mouse; Heat shock protein; Hypoxia; heat shock proteins
• DOI: 10.1152/japplphysiol.01324.2004
• ISSN: 8750-7587

1 Department of Sport Biology, Faculty of Sport Science, and 2 Department of Clinical Analysis and of Biochemistry, Faculty of Pharmacy, Institute for Molecular and Cell Biology University of Porto, Porto, Portugal Submitted 24 November 2004 ; accepted in final form 11 May 2005 ABSTRACT Severe high-altitude hypoxia exposure is considered a triggering stimulus for redox disturbances at distinct levels of cellular organization. The effect of an in vivo acute and severe hypobaric hypoxic insult (48 h at a pressure equivalent to 8,500 m) on oxidative damage and respiratory function was analyzed in skeletal muscle mitochondria isolated from vitamin E-supplemented (60 mg/kg ip, 3 times/wk for 3 wk) and nonsupplemented mice. Forty male mice were randomly divided into four groups: control + placebo, hypoxia + placebo (H + P), control + vitamin E, and hypoxia + vitamin E. Significant increases in mitochondrial heat shock protein 60 expression and protein carbonyls group levels and decreases in aconitase activity and sulfhydryl group content were found in the H + P group when compared with the control + placebo group. Mitochondrial respiration was significantly impaired in animals from the H + P group, as demonstrated by decreased state 3 respiratory control ratio and ADP-to-oxygen ratio and by increased state 4 with both complex I- and II-linked substrates. Using malate + pyruvate as substrates, hypoxia decreased the respiratory rate in the presence of carbonyl cyanide m -chlorophenylhydrazone and also stimulated oligomycin-inhibited respiration. However, vitamin E treatment attenuated the effect of hypoxia on the mitochondrial levels of heat shock protein 60 and markers of oxidative stress. Vitamin E was also able to prevent most mitochondrial alterations induced by hypobaric hypoxia. In conclusion, hypobaric hypoxia increases mitochondrial oxidative stress while decreasing mitochondrial capacity for oxidative phosphorylation. Vitamin E was an effective preventive agent, which further supports the oxidative character of mitochondrial dysfunction induced by hypoxia. high altitude; oxidative damage; antioxidants; heat shock proteins; vitamin E Address for reprint requests and other correspondence: J. Magalhães, Faculty of Sport Sciences, Dept. of Sport Biology, Univ. of Porto, Rua Dr. Plácido Costa, 91, 4200-450 Porto, Portugal (E-mail: jmaga{at}fcdef.up.pt )