title: Training-induced mitochondrial adaptation: role of peroxisome proliferator-activated receptor γ coactivator-1α, nuclear factor-κB and β-blockade.
abstract: Interaction of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) with other cellular signalling pathways plays an important role in training-induced mitochondrial adaptations. The purpose of this study was to examine whether pyrolidine dithiocarbamate (PDTC), a nuclear factor-κB inhibitor and antioxidant, and the β-adrenergic blocker propranolol would affect the PGC-1α-induced mitochondrial transcription factors, enzymes and proteins involved in energy metabolism and antioxidant defense in response to endurance training. Female Sprague-Dawley rats (aged 8 weeks) were randomly divided into two groups (n = 24), one subjected to 8 weeks of treadmill training and one remaining sedentary. Each group of rats was subdivided in to three groups that were injected (i.p.) daily with PDTC (50 mg (kg body weight)(-1)), propranolol (30 mg kg(-1)) or saline as a control 1 h before the daily exercise session. Sedentary PDTC-treated rats showed 75% higher PGC-1α content (P < 0.01) but lower mitochondrial transcription factor A and phosphorylated cAMP-responsive element binding protein (p-CREB) than control rats. Training increased PGC-1α by 57% (P < 0.01), cytochrome c oxidase 4 by 30% (P < 0.05) and p-CREB by 13% (P < 0.05), whereas the mitochondrial mitofusin-2 level was decreased by 24% (P < 0.01). Treatment with PDTC decreased PGC-1α and p-CREB content by 34 and 53% (P < 0.05), respectively, in trained rats and abolished training effects on cytochrome c oxidase 4 and mitochondrial mitofusin-2. None of the training effects was abolished by propranolol treatment. Mitochondrial superoxide dismutase activity was decreased with PDTC, whereas training-induced glutathione peroxidase activity was unaltered by either drug. The data indicates that nuclear factor-κB-inhibitory and antioxidant properties of PDTC can attenuate PGC-1α-mediated mitochondrial adaptation to endurance training, whereas the β-adrenergic pathway has little adverse effect.
authors.affiliation: Laboratory of Physiological Hygiene and Exercise Science, University of Minnesota, 1900 University Avenue, Minneapolis, MN 55455, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Feng
authors.forename: Chounghun
authors.initials: C
authors.lastname: Kang
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dickman
authors.forename: Ryan
authors.initials: R
authors.lastname: Koenig
authors.forename: Iwalola
authors.initials: I
authors.lastname: Awoyinka
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li Li
authors.initials: LL
authors.lastname: Ji
mesh_terms: D000222:Adaptation, Physiological; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004268:DNA-Binding Proteins; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D020558:GTP Phosphohydrolases; D008565:Membrane Proteins / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D000319:Adrenergic beta-Antagonists; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D011759:Pyrrolidines; D016601:RNA-Binding Proteins; D013859:Thiocarbamates; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; C020972:pyrrolidine dithiocarbamic acid; D011433:Propranolol; D003576:Electron Transport Complex IV; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat