title: Exercise training decreases rat heart mitochondria free radical generation but does not prevent Ca2+-induced dysfunction.
abstract: Exercise provides cardioprotection against ischemia-reperfusion injury, a process involving mitochondrial reactive oxygen species (ROS) generation and calcium overload. This study tested the hypotheses that isolated mitochondria from hearts of endurance-trained rats have decreased ROS production and improved tolerance against Ca(2+)-induced dysfunction. Male Fischer 344 rats were either sedentary (Sed, n = 8) or endurance exercise trained (ET, n = 11) by running on a treadmill for 16 wk (5 days/wk, 60 min/day, 25 m/min, 6 degrees grade). Mitochondrial oxidative phosphorylation measures were determined with glutamate-malate or succinate as substrates, and H(2)O(2) production and permeability transition pore (PTP) opening were determined with succinate. All assays were carried out in the absence and presence of calcium. In response to 25 and 50 microM CaCl(2), Sed and ET displayed similar decreases in state 3 respiration, respiratory control ratio, and ADP:O ratio. Ca(2+)-induced PTP opening was also similar. However, H(2)O(2) production by ET was lower than Sed (P < 0.05) in the absence of calcium (323 +/- 12 vs. 362 +/- 11 pmol.min(-1).mg protein(-1)) and the presence of 50 microM CaCl(2) (154 +/- 3 vs. 197 +/- 7 pmol.min(-1).mg protein(-1)). Rotenone, which blocks electron flow from succinate to complex 1, reduced H(2)O(2) production and eliminated differences between ET and Sed. Mitochondrial superoxide dismutase and glutathione peroxidase were not affected by exercise. Catalase activity was extremely low but increased 49% in ET (P < 0.05). In conclusion, exercise reduces ROS production in myocardial mitochondria through adaptations specific to complex 1 but does not improve mitochondrial tolerance to calcium overload.
authors.affiliation: Dept. of Kinesiology and Health Education, The University of Texas at Austin, Austin, TX 78712-0360, USA. jstarnes@mail.utexas.edu
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Starnes
authors.forename: Brian D
authors.initials: BD
authors.lastname: Barnes
authors.forename: Marissa E
authors.initials: ME
authors.lastname: Olsen
mesh_terms: D000222:Adaptation, Physiological; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide; D008293:Malates / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D010807:Physical Endurance; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012402:Rotenone / Q000494:pharmacology; D019802:Succinic Acid / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D008293:Malates; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D012402:Rotenone; D018698:Glutamic Acid; D000244:Adenosine Diphosphate; C030298:malic acid; D019802:Succinic Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D042967:Electron Transport Complex I; D010100:Oxygen; D002118:Calcium