title: Exercise-induced adaptations of cardiac redox homeostasis and remodeling in heterozygous SOD2-knockout mice.
abstract: A reduced expression of the manganese-dependent superoxide dismutase (SOD2) is characterized by increased cardiac oxidative stress. Oxidative stress has also been described in situations of physical exercise. We investigated the influence of physical exercise (EX; treadmill 1 h/day at 15 m/min, 5 days/wk, at an angle of 5° for a duration of 8 wk) on cardiac function [heart frequency (HF), echocardiography, morphometry], oxidative stress [reactive oxygen species (ROS)], and antioxidative defence capacity (peroxiredoxin 1-6) in male SOD2-knockout (SOD2_EX) and wild-type mice (WT_EX) compared with untrained age-matched animals (WT_CON; SOD2_CON). In SOD2_CON, heart weight, cardiomyocyte diameter, and cardiac ROS were significantly larger and peroxiredoxin isoforms 4-6 lower than in WT_CON. The vessel-to-cardiomyocyte ratio, cardiac VEGF-concentration, and cardiac function were similar in SOD2_CON and WT_CON. Both groups tolerated the exercise protocol well. In WT, exercise significantly increased vessel-to-cardiomyocyte ratio and ROS-generation and downregulated peroxiredoxin isoforms 4-6 and VEGF generation. The vessel-to-cardiomyocyte ratio, cardiac VEGF concentration, and cardiac ROS were not altered in SOD2_EX compared with SOD2_CON, but a significant upregulation of cardiac peroxiredoxin 1 and 4 was observed. Similar to the result observed in WT_EX, peroxiredoxin 3 was upregulated in SOD2_EX. Chronic exercise shifted the (mal)adaptive hypertrophic into a compensated dilated cardiac phenotype in SOD2_EX. In conclusion, downregulation of SOD2 induces a maladaptive cardiac hypertrophy. In this situation, physical exercise results in a further deterioration of cardiac remodeling despite an upregulation of the antioxidative defense system.
authors.affiliation: Dept. of Molecular and Cellular Sport Medicine, German Sport Univ. Cologne, Carl-Diem-Weg 6, 50933 Cologne, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Richters
authors.forename: N
authors.initials: N
authors.lastname: Lange
authors.forename: R
authors.initials: R
authors.lastname: Renner
authors.forename: N
authors.initials: N
authors.lastname: Treiber
authors.forename: A
authors.initials: A
authors.lastname: Ghanem
authors.forename: K
authors.initials: K
authors.lastname: Tiemann
authors.forename: K
authors.initials: K
authors.lastname: Scharffetter-Kochanek
authors.forename: W
authors.initials: W
authors.lastname: Bloch
authors.forename: K
authors.initials: K
authors.lastname: Brixius
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation; D006321:Heart / Q000502:physiology*; D006579:Heterozygote; D006706:Homeostasis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D054464:Peroxiredoxins / Q000235:genetics; D010805:Physical Conditioning, Animal / Q000502:physiology*; D020033:Protein Isoforms; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D020257:Ventricular Remodeling / Q000235:genetics / Q000502:physiology*; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D054464:Peroxiredoxins; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D042461:Vascular Endothelial Growth Factor A; D000099156:Superoxide Dismutase 2; C467480:vascular endothelial growth factor A, mouse