Training-induced mitochondrial adaptation: role of peroxisome proliferator-activated receptor γ coactivator-1α,...

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.