Exercise activation of muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling is redox sensitive.

The peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha)-activated signal transduction pathway has previously been shown to stimulate mitochondrial biogenesis in skeletal muscle in response to endurance exercise. In vitro data indicate that PGC-1alpha signaling may be sensitive to reactive oxygen species (ROS) but its role in vivo is not clear. The objectives of this study were (1) to investigate whether the PGC-1alpha pathway could be activated by a single bout of anaerobic exercise in rats, wherein a major portion of ROS was generated via the cytosolic xanthine oxidase (XO), and (2) to examine whether allopurinol (ALP), a specific XO inhibitor, would attenuate PGC-1alpha expression and signaling owing to decreased ROS generation. Female Sprague-Dawley rats were randomly divided into three groups: (1) subjected to sprinting on a treadmill at 35 m/min, 15% grade, for 3 min followed by 3 min slow running at 15 m/min, 0% grade, repeated until exhaustion (88 +/- 4 min; Exer; N= 9); (2) subjected to the same exercise protocol (88 +/- 4 min) but injected with two doses of ALP (0.4 mmol/kg, ip) 24 and 1 h before the experiment (Exer+ ALP; N= 9); and (3) rested control (C; N= 9). Exercise increased XO activity and ROS generation in the Exer rat vastus lateralis muscle (P< 0.05), whereas the Exer+ ALP group displayed only 7% XO activity and similar ROS level compared with the C group. PGC-1alpha protein content showed a 5.6-fold increase (P< 0.01) in Exer vs C, along with a 200% (P< 0.01) increase in both nuclear respiratory factor (NRF)-1 and mitochondrial transcription factor A (Tfam) content. ALP treatment decreased PGC-1alpha, NRF-1, and Tfam levels by 45, 19, and 20% (P< 0.05), respectively. Exercise doubled the content of the phosphorylated cAMP-responsive element-binding protein in the Exer group (P< 0.01) and tripled phosphorylated p38 mitogen-activated protein kinase (P< 0.01), whereas these effects were reduced by 60 and 30% (P< 0.01, P< 0.05), respectively, in Exer+ ALP rats. Nuclear factor-kappaB binding and phospho-IkappaB content were also increased in Exer rats (P< 0.01) and these increases were abolished by ALP treatment. The data indicate that contraction-activated PGC-1alpha signaling pathways in skeletal muscle are redox sensitive and that nonmitochondrial ROS play an important role in stimulating mitochondrial biogenesis.

Rapid IV versus oral rehydration: responses to subsequent exercise heat stress.

PURPOSE: This study sought to determine the effect of rapid intravenous (IV) versus oral (ORAL) rehydration immediately after dehydration, on cardiovascular, thermoregulatory, and perceptual responses during subsequent exercise in the heat. METHODS: Eight males (21.4 +/- 0.7 yr; 176.2 +/- 1.6 cm; 75.2 +/- 3.7 kg; 63.7 +/- 3.6 mL.kg.min VO2max, 9.0 +/- 1.7% fat) participated in three randomized trials. Each trial consisted of a 75-min dehydration phase (36 degrees C; 42.5% rh, 47 +/- 0.9% VO2max) where subjects lost 1.7 L (IV and no-fluid (NF) trials) to 1.8 L of fluid (ORAL trial). In the heat, fluid lost was matched with 0.45% saline in 20 min by either IV or ORAL rehydration; no fluid was given in the NF trial. Subjects then performed a heat-tolerance test (HTT; 37.0 degrees C, 45% rh, treadmill speed of 2.4 m.s, 2.3% grade) for 75 min or until exhaustion (Tre of 39.5 degrees C). During the HTT, thermal and thirst sensations, RPE, rectal temperature (Tre), heart rate (HR), and mean weighted skin temperature (Tsk) were measured. RESULTS: Plasma volume in the IV treatment was greater (P < 0.05) after rehydration compared with ORAL and NF. However, during the HTT there were no overall differences (P > 0.05) in HR, Tre, Tsk, RPE, thermal sensations, or HTT time (ORAL, 71 +/- 8 min; IV, 73 +/- 5 min; NF, 39 +/- 29 min) between the ORAL and IV treatments. Sensations of thirst were lower (P < 0.05) in ORAL compared with IV and NF, likely because of oropharyngeal stimuli. CONCLUSIONS: Despite a more rapid restoration of plasma volume, IV rehydration was not advantageous over ORAL rehydration in regards to physiological strain, heat tolerance, RPE, or thermal sensations.