title: Exercise can induce temporary mitochondrial and contractile dysfunction linked to impaired respiratory chain complex activity.
abstract: Exercise is considered to elicit a physiological response of the heart. Previous studies investigated the influence of repetitive exercise only at the end of the training period. We assessed the impact of 2 exercise protocols, differing in their treadmill inclination, on cardiac and mitochondrial function at different times during the training period. Within 10 weeks, animals trained with 16% incline developed hypertrophy (left ventricular posterior wall thickness: 1.6 ± 0.1 vs 2.4 ± 0.1 mm; P < .05) with normal function (ejection fraction: 75.2% ± 2.5% vs 75.6% ± 2.1%). However, at 6 weeks, there was temporary impairment of contractile function (ejection fraction: 74.5% ± 1.67% vs 65.8% ± 2.3%; P < .05) associated with decreased mitochondrial respiratory capacity (state 3 respiration: 326 ± 71 vs 161 ± 22 natoms/[min mg protein]; P < .05) and a gene expression shift from the adult (α) to the fetal (β) myosin heavy chain isoform. Although peroxisome proliferator-activated receptor gamma coactivator-1α expression was normal, nuclear respiratory factors (NRFs)-1 and -2 were significantly reduced (NRF-1: 1.00 ± 0.16 vs 0.55 ± 0.09; NRF-2: 1.00 ± 0.11 vs 0.63 ± 0.07; P < .05) after 6 weeks. These findings were associated with a reduction of electron transport chain complexes I and IV activity (complex I: 1016 ± 67 vs 758 ± 71 nmol/[min mg protein]; complex IV: 18768 ± 1394 vs 14692 ± 960 nmol/[min mg protein]; P < .05). Messenger RNA expression of selected nuclear encoded subunits of the electron transport chain was unchanged at all investigated time points. In contrast, animals trained with 10% incline showed less hypertrophy and normal function in echocardiography, normal maximal respiratory capacity, and unchanged complex activities at all 3 time points. Repetitive exercise may cause contractile and mitochondrial dysfunction characterized by impaired respiratory chain complex activities. This activity reduction is temporary and intensity related.
authors.affiliation: Department of Cardiac Surgery, Heart Center Leipzig, University of Leipzig, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Schoepe
authors.forename: Andrea
authors.initials: A
authors.lastname: Schrepper
authors.forename: Michael
authors.initials: M
authors.lastname: Schwarzer
authors.forename: Moritz
authors.initials: M
authors.lastname: Osterholt
authors.forename: Torsten
authors.initials: T
authors.lastname: Doenst
mesh_terms: D000818:Animals; D019069:Cell Respiration / Q000235:genetics / Q000502:physiology; D004579:Electron Transport / Q000235:genetics / Q000502:physiology*; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D051268:GA-Binding Protein Transcription Factor / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D008297:Male; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000378:metabolism
chemical_list: D051268:GA-Binding Protein Transcription Factor; C000594638:MYH7 protein, rat; D051266:Nuclear Respiratory Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D003576:Electron Transport Complex IV; D018995:Myosin Heavy Chains; D042967:Electron Transport Complex I