Jonathan R. Dickman

Exercise activation of muscle peroxisome proliferator-activated receptor-γ coactivator-1α 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.

Avenanthramides are bioavailable and accumulate in hepatic, cardiac, and skeletal muscle tissue following oral gavage in rats.

Avenanthramides (AVA), polyphenols found exclusively in oats ( Avena sativa L.), may play a role in the anti-inflammatory and antiatherogenic activity of oats. The bioavailability of AVA has been demonstrated previously, but its distribution at the organ and tissue level and the extent of conjugation following ingestion have been unexplored. Synthetic AVA was administered to 24 rats by oral gavage, whereas 6 control rats received saline. AVA concentrations were measured via HPLC in plasma, liver, heart, and gastrocnemius (GAS) obtained over a 12 h period (0, 2, 4, 12 h; n = 6 at each time point). Samples were extracted with and without glucuronidase-sulfatase to assess the level of conjugation. We conclude that AVA are bioavailable to the blood circulation following oral ingestion in the rat and reach peripheral tissues where they can be taken up by various organs differentially. With AVA remaining in the organs for up to 12 h, it seems possible to maintain an increased level of AVA in the rat via repeated feedings.

Exercise-Induced Hormesis May Help Healthy Aging

Hormesis plays a critical role in producing some major benefits derived from physical exercise. However whether these known cellular mechanisms are applicable to ameliorate age-related deterioration of muscle function is not entirely clear. The present communication proposes that antioxidant adaptation, the peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α activated mitochondrial biogenesis, and eccentric contraction-induced, cytokine-propelled muscle inflammation could be important redox-sensitive pathways by which exercise-induced disturbance in oxidant-antioxidant hemeostasis may serve as a heretic stimulus to promote adaptations that help healthy aging and improve the quality of life.

Training-induced mitochondrial adaptation: role of peroxisome proliferator-activated receptor γ coactivator-1α, nuclear factor-κB and β-blockade

•  What is the central question of this study? The peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) signalling pathway plays an important role in mitochondrial biogenesis and has been shown to be activated both by an acute bout of exercise and by long‐term training. However, the upstream signals and control mechanisms causing the adaptation and its interaction with other signalling pathways during exercise are not clear. •  What is the main finding and its importance? Our main finding was that PGC‐1α‐controlled mitochondrial training adaptation was attenuated by pyrolidine dithiocarbamate, an antioxidant known to block nuclear factor‐κB signalling, which indicates that PGC‐1α signalling is redox sensitive and can be influenced by nuclear factor‐κB. We also found that the β‐adrenergic blocker propranolol did not prevent the training‐induced adaptation of muscle mitochondrial protein under our experimental conditions.

American Ginseng Supplementation Induces an Oxidative Stress in Postmenopausal Women

Objective: To determine whether American ginseng (Panax Quinquefolium) confers antioxidant protection to postmenopausal women at rest and after a mild aerobic exercise session. Methods: In this double-blinded parallel study, 12 female subjects (age range 55–75) consumed two capsules, containing 500 mg of dry American ginseng whole-root powder, everyday for 4 months, whereas 13 female control subjects of the same age range consumed two placebo capsules. Before and after the supplementation regimen each subject performed 30 minutes of treadmill walking on a 5% grade incline at an estimated 60% of VO2max. Results: Ginseng supplementation had no effect on heart rate, blood pressure, plasma blood glucose, or lactate concentration at rest or immediately after exercise tests. The ginseng supplemented group displayed a higher resting plasma glutathione disulfide (GSSG) concentration and lower glutathione (GSH):GSSG ratio, as well as a lower resting total antioxidant content (TAC). Plasma GSSG concentration decreased, whereas the GSH:GSSG ratio and TAC increased after exercise in all subjects. Furthermore, plasma malondialdehyde and urine 8-hydroxydeoxyguanosine concentrations were elevated in the ginseng-supplemented group. Erythrocyte superoxide dismutase and GSH reductase activities were increased after ginseng supplementation. The 30-minute treadmill walking, however, did not alter these changes. Conclusions: These data suggest that chronic American ginseng supplementation at the given dose can cause an oxidative stress in postmenopausal women, as reflected by the elevated oxidative damage markers and the increased erythrocyte antioxidant enzyme activity.