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Prolonged immobilization (IM) causes skeletal muscle atrophy characterized by mitochondrial deterioration and proteolysis. Muscle remobilization (RM) increases reactive oxygen species generation, proinflammatory cytokine expression, and oxidative stress, preventing muscle from quick recovery. Thus, we hypothesized that overexpression of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) via in vivo transfection would promote mitochondrial biogenesis and antioxidant defense, thus ameliorating the aforementioned deteriorations in a mouse model with 14-d IM followed by 5-d RM. PGC-1α transfection in tibialis anterior muscle resulted in a 7.2- and 4-fold increase in PGC-1α content in cytosol and nucleus, respectively. Mitochondrial biogenic (cytochrome c, mitochondrial transcription factor A), morphologic (mitochondrial density, mDNA/nDNA ratio), and functional (cytochrome c oxidase activity, ATP synthesis rate) markers, as well as fiber cross-sectional area, significantly increased in IM-RM muscle by PGC-1α overexpression. These effects were accompanied by an 18% decrease in H2O2, 30% decrease in nuclear factor-κB-DNA binding, and 25% reduction of IL-1β and-6 production in IM-RM muscle. There was a 34% increase in superoxide dismutase-2 activity, along with a 3.5-fold increase in NAD-dependent deacetylase sirtuin-3 expression caused by enhanced PGC-1α-estrogen-related receptor α binding. Our findings highlighted the importance of PGC-1α in protecting muscle from metabolic and redox disturbances caused by IM. [ABSTRACT FROM AUTHOR]

Reactive oxygen or nitrogen species (RONS) are produced during exercise due, at least in part, to the activation of xanthine oxidase. When exercise is exhaustive they cause tissue damage; however, they may also act as signals inducing specific cellular adaptations to exercise. We have tested this hypothesis by studying the effects of allopurinol-induced inhibition of RONS production on cell signalling pathways in rats submitted to exhaustive exercise. Exercise caused an activation of mitogen-activated protein kinases (MAPKs: p38, ERK 1 and ERK 2), which in turn activated nuclear factor κB (NF-κB) in rat gastrocnemius muscle. This up-regulated the expression of important enzymes associated with cell defence (superoxide dismutase) and adaptation to exercise (eNOS and iNOS). All these changes were abolished when RONS production was prevented by allopurinol. Thus we report, for the first time, evidence that decreasing RONS formation prevents activation of important signalling pathways, predominantly the MAPK–NF-κB pathway; consequently the practice of taking antioxidants before exercise may have to be re-evaluated. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor γ co-activator 1 α (PGC-1) is a potent stimulator of mitochondrial biogenesis in skeletal muscle. The interaction of PGC-1 and nuclear respiratory factor (NRF-1) is critical in mitochondrial transcription factor A (mtTFA) expression. The objective of the current study is two-fold: (a) to investigate whether acute exercise induces PGC-1 and related TFs; (b) to examine the role of reactive oxygen species (ROS) in PGC-1 expression and signaling. Female Sprague-Dawley rats were randomly divide into 3 groups: (1) sprinting on treadmill at 35 m/min, 15% grade, for 3 min followed by 3 min rest, repeated until exhaustion (88±4 min; ST, N=9); (2) subjected to ST (88±4 min) and two i.p. injections of allopurinol (0.4 mmol/kg each) 24 and 1 h before ST (ALP, N=9); and (3) rested control (C, N=9). Concentration of PGC-1 in vastus lateralis muscle was 7-fold higher in ST vs. C (P<0.01), but unaltered in ALP. Both NRF-1 and mtTFA contents were elevated 2-fold in ST (P<0.05), but not in ALP. cAMP-responsive element-binding protein (CREB) level was not affected by exercise or ALP. The data suggest ROS play a role in regulating exercise-induced mitochondrial biogenic pathway. [ABSTRACT FROM AUTHOR]

Gene regulation of antioxidant enzymes is known to be regulated via redox-sensitive signal transduction pathways involving nuclear factor (NF) kappaB and mitogen-activated protein kinases (MAPK). The purpose of this study is to examine whether pharmacological inhibition of NFkB and MAPK attenuates training-induced antioxidant adaptation in heart and skeletal muscle. Female Sprague-Dawley rats were injected (i.p.) daily with either NFkB inhibitor pyrolidine dithiocarbamate (PDTC, 50 mg/kg, N=8), beta-adrenergic blocker propranolol (PL, 30 mg/kg, N=8), or saline (S, N=8) during an 8-wk treadmill training regimen at 26 m/min, 15% grade for 1 h/day, 5 d/wk. Matching sedentary control rats (N=8) were treated with equal doses of respective drugs or saline. Rats were killed at resting state. Manganese superoxide disumutase activity was decreased in vastus lateralis muscle but elevated in heart with PDTC. Glutathione peroxidase activity increased with training, but lowered with PDTC. Malodialdehyde content declined with training but increased with PDTC in heart and two muscles. The data suggests impaired NFkB activity by PDTC may affect antioxidant expression and induce oxidative stress. [ABSTRACT FROM AUTHOR]

Avenanthramides (Avn) are antioxidants found exclusively in oats (Arena sativa L.). The aim of this study was to determine the time course of Avn absorption into plasma and liver following their ingestion. Avn Bp, Bf, and Bc (20 mg/kg body wt) were fed to female Sprague-Dawley rats (N=20) by oral gavage. Plasma and liver samples were collected at 1, 2, 4, and 12 h post-gavage and analyzed with HPLC. Bp was the most abundant in the plasma at all time points, reaching peak concentration of 0.698 ppm. In the liver, Bp reached peak concentration of 7.236 µg/mg liver at 4 h. Plasma Bf was elevated at 1 and 2 h before declining at 4 h. Bc concentration peaked at 0.177 ppm in the plasma at 1 h and returned to zero by 12 h, but remained elevated in the liver over the entire time course. At 12 h, only Bp remained bioavailable, whereas all three Avn fractions were present in the liver. We conclude that rats have the ability to store Avn despite their elimination from the circulation during the 12-h post-absorptive period. [ABSTRACT FROM AUTHOR]