scholarly journals Increased oxidative stress and anaerobic energy release, but blunted Thr172-AMPKα phosphorylation, in response to sprint exercise in severe acute hypoxia in humans

2012 ◽  
Vol 113 (6) ◽  
pp. 917-928 ◽  
Author(s):  
David Morales-Alamo ◽  
Jesús Gustavo Ponce-González ◽  
Amelia Guadalupe-Grau ◽  
Lorena Rodríguez-García ◽  
Alfredo Santana ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vastus Lateralis ◽  
Acute Hypoxia ◽  
Sirtuin 1 ◽  
Vastus Lateralis Muscle ◽  
Mean Power ◽  
Muscle Lactate ◽  
Sprint Exercise ◽  
Akt Phosphorylation ◽  
Exercise Response

AMP-activated protein kinase (AMPK) is a major mediator of the exercise response and a molecular target to improve insulin sensitivity. To determine if the anaerobic component of the exercise response, which is exaggerated when sprint is performed in severe acute hypoxia, influences sprint exercise-elicited Thr172-AMPKα phosphorylation, 10 volunteers performed a single 30-s sprint (Wingate test) in normoxia and in severe acute hypoxia (inspired Po2: 75 mmHg). Vastus lateralis muscle biopsies were obtained before and immediately after 30 and 120 min postsprint. Mean power output and O2 consumption were 6% and 37%, respectively, lower in hypoxia than in normoxia. O2 deficit and muscle lactate accumulation were greater in hypoxia than in normoxia. Carbonylated skeletal muscle and plasma proteins were increased after the sprint in hypoxia. Thr172-AMPKα phosphorylation was increased by 3.1-fold 30 min after the sprint in normoxia. This effect was prevented by hypoxia. The NAD+-to-NADH.H+ ratio was reduced (by 24-fold) after the sprints, with a greater reduction in hypoxia than in normoxia ( P < 0.05), concomitant with 53% lower sirtuin 1 (SIRT1) protein levels after the sprint in hypoxia ( P < 0.05). This could have led to lower liver kinase B1 (LKB1) activation by SIRT1 and, hence, blunted Thr172-AMPKα phosphorylation. Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation, a known negative regulating mechanism of Thr172-AMPKα phosphorylation, was increased by 60% immediately after the sprint in hypoxia, coincident with increased Thr308-Akt phosphorylation. Collectively, our results indicate that the signaling response to sprint exercise in human skeletal muscle is altered in severe acute hypoxia, which abrogated Thr172-AMPKα phosphorylation, likely due to lower LKB1 activation by SIRT1.

scholarly journals Skeletal muscle signaling, metabolism, and performance during sprint exercise in severe acute hypoxia after the ingestion of antioxidants

2017 ◽  
Vol 123 (5) ◽  
pp. 1235-1245 ◽  
Author(s):  
David Morales-Alamo ◽  
Borja Guerra ◽  
Jesús Gustavo Ponce-González ◽  
Amelia Guadalupe-Grau ◽  
Alfredo Santana ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Transforming Growth Factor ◽  
Vastus Lateralis ◽  
Acute Hypoxia ◽  
Molar Ratio ◽  
Vastus Lateralis Muscle ◽  
Sprint Exercise ◽  
Amp Activated Protein Kinase ◽  
Glycolytic Rate

The aim of this study was to determine if reactive oxygen species (ROS) could play a role in blunting Thr172-AMP-activated protein kinase (AMPK)-α phosphorylation in human skeletal muscle after sprint exercise in hypoxia and to elucidate the potential signaling mechanisms responsible for this response. Nine volunteers performed a single 30-s sprint (Wingate test) in two occasions while breathing hypoxic gas ([Formula: see text] = 75 mmHg): one after the ingestion of placebo and another following the intake of antioxidants (α-lipoic acid, vitamin C, and vitamin E), with a randomized double-blind design. Vastus lateralis muscle biopsies were obtained before, immediately after, and 30- and 120-min postsprint. Compared with the control condition, the ingestion of antioxidants resulted in lower plasma carbonylated proteins, attenuated elevation of the AMP-to-ATP molar ratio, and reduced glycolytic rate ( P < 0.05) without significant effects on performance or V̇o2. The ingestion of antioxidants did not alter the basal muscle signaling. Thr172-AMPKα and Thr184/187-transforming growth factor-β-activated kinase 1 (TAK1) phosphorylation were not increased after the sprint regardless of the ingestion of antioxidants. Thr286-CaMKII phosphorylation was increased after the sprint, but this response was blunted by the antioxidants. Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation increased immediately after the sprints coincident with increased Akt phosphorylation. In summary, antioxidants attenuate the glycolytic response to sprint exercise in severe acute hypoxia and modify the muscle signaling response to exercise. Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation, a known mechanism of Thr172-AMPKα phosphorylation inhibition, is increased immediately after sprint exercise in hypoxia, probably by a mechanism independent of ROS. NEW & NOTEWORTHY The glycolytic rate is increased during sprint exercise in severe acute hypoxia. This study showed that the ingestion of antioxidants before sprint exercise in severe acute hypoxia reduced the glycolytic rate and attenuated the increases of the AMP-to-ATP and the reduction of the NAD+-to-NADH.H+ ratios. This resulted in a modified muscle signaling response with a blunted Thr286-CaMKII but similar AMP-activated protein kinase phosphorylation responses in the sprints preceded by the ingestion of antioxidants.

Phosphorylase a in human skeletal muscle during exercise and electrical stimulation

1978 ◽  
Vol 45 (6) ◽  
pp. 852-857 ◽  
Author(s):  
P. D. Gollnick ◽  
J. Karlsson ◽  
K. Piehl ◽  
B. Saltin
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Muscular Activity ◽  
Voluntary Exercise ◽  
Vastus Lateralis Muscle ◽  
Minor Importance ◽  
Muscle Lactate ◽  
Needle Technique

Experiments were conducted to examine the conversions of phosphorylase b to phosphorylase a in human skeletal muscle during bicycle exercise or isometric contractions. Muscle biopsies were obtained from the vastus lateralis with the needle technique at rest and either during or immediately after activity and frozen in liquid nitrogen within 2--4 s. Total phosphorylase and phosphorylase a activities were differentiated by measurement in the presence and absence of AMP, respectively. At rest 8.5% of the total phosphorylase activity existed in the a form. Little or no change in the percent of phosphorylase in the a form occurred during voluntary dynamic or static muscular activity that produced muscle lactate concentrations in excess of 18 mmol.kg-1 wet muscle. Electrical stimulation of the vastus lateralis muscle also failed to produce an increase in the percentage of phosphorylase a. These data suggest that during exercise the conversion of phosphorylase to the a form is of minor importance. An increased activity of phosphorylase b due to changes in muscle concentrations of ATP, AMP, and inorganic phosphate may regulate glycogenolysis during voluntary exercise in man.

scholarly journals Antioxidants Facilitate High–intensity Exercise IL–15 Expression in Skeletal Muscle

2018 ◽  
Vol 40 (01) ◽  
pp. 16-22 ◽  
Author(s):  
Alberto Pérez-López ◽  
Marcos Martin-Rincon ◽  
Alfredo Santana ◽  
Ismael Perez-Suarez ◽  
Cecilia Dorado ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
High Intensity ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Acute Hypoxia ◽  
High Intensity Exercise ◽  
Oxygen Deficit ◽  
Post Exercise ◽  
Sprint Exercise

AbstractInterleukin (IL)-15 stimulates mitochondrial biogenesis, fat oxidation, glucose uptake and myogenesis in skeletal muscle. However, the mechanisms by which exercise triggers IL-15 expression remain to be elucidated in humans. This study aimed at determining whether high-intensity exercise and exercise-induced RONS stimulate IL-15/IL-15Rα expression and its signaling pathway (STAT3) in human skeletal muscle. Nine volunteers performed a 30-s Wingate test in normoxia and hypoxia (PIO2=75 mmHg), 2 h after placebo or antioxidant administration (α-lipoic acid, vitamin C and E) in a randomized double-blind design. Blood samples and muscle biopsies (vastus lateralis) were obtained before, immediately after, and 30 and 120 min post-exercise. Sprint exercise upregulated skeletal muscle IL-15 protein expression (ANOVA, P=0.05), an effect accentuated by antioxidant administration in hypoxia (ANOVA, P=0.022). In antioxidant conditions, the increased IL-15 expression at 120 min post-exercise (33%; P=0.017) was associated with the oxygen deficit caused by the sprint (r=–0.54; P=0.020); while, IL-15 and Tyr705-STAT3 AUCs were also related (r=0.50; P=0.036). Antioxidant administration promotes IL-15 protein expression in human skeletal muscle after sprint exercise, particularly in severe acute hypoxia. Therefore, during intense muscle contraction, a reduced PO2 and glycolytic rate, and possibly, an attenuated RONS generation may facilitate IL-15 production, accompanied by STAT3 activation, in a process that does not require AMPK phosphorylation.

scholarly journals Human muscle metabolism during intermittent maximal exercise

1993 ◽  
Vol 75 (2) ◽  
pp. 712-719 ◽  
Author(s):  
G. C. Gaitanos ◽  
C. Williams ◽  
L. H. Boobis ◽  
S. Brooks
Keyword(s):  
Power Output ◽  
Maximal Exercise ◽  
Vastus Lateralis ◽  
Lactate Concentration ◽  
High Plasma ◽  
Cycle Ergometer ◽  
Vastus Lateralis Muscle ◽  
Mean Power ◽  
Muscle Lactate ◽  
Atp Production

Eight male subjects volunteered to take part in this study. The exercise protocol consisted of ten 6-s maximal sprints with 30 s of recovery between each sprint on a cycle ergometer. Needle biopsy samples were taken from the vastus lateralis muscle before and after the first sprint and 10 s before and immediately after the tenth sprint. The energy required to sustain the high mean power output (MPO) that was generated over the first 6-s sprint (870.0 +/- 159.2 W) was provided by an equal contribution from phosphocreatine (PCr) degradation and anaerobic glycolysis. Indeed, within the first 6-s bout of maximal exercise PCr concentration had fallen by 57% and muscle lactate concentration had increased to 28.6 mmol/kg dry wt, confirming significant glycolytic activity. However, in the tenth sprint there was no change in muscle lactate concentration even though MPO was reduced only to 73% of that generated in the first sprint. This reduced glycogenolysis occurred despite the high plasma epinephrine concentration of 5.1 +/- 1.5 nmol/l after sprint 9. In face of a considerable reduction in the contribution of anaerobic glycogenolysis to ATP production, it was suggested that, during the last sprint, power output was supported by energy that was mainly derived from PCr degradation and an increased aerobic metabolism.

Muscle glycogen availability and temperature regulation in humans

1989 ◽  
Vol 66 (1) ◽  
pp. 72-78 ◽  
Author(s):  
L. Martineau ◽  
I. Jacobs
Keyword(s):  
Skeletal Muscle ◽  
Muscle Glycogen ◽  
Temperature Regulation ◽  
Vastus Lateralis ◽  
Water Immersion ◽  
Vastus Lateralis Muscle ◽  
Glycogen Concentration ◽  
Exercise Regimen ◽  
Before And After ◽  
Muscle Groups

The effects of intramuscular glycogen availability on human temperature regulation were studied in eight seminude subjects immersed in 18 degrees C water for 90 min or until rectal temperature (Tre) decreased to 35.5 degrees C. Each subject was immersed three times over a 3-wk period. Each immersion followed 2.5 days of a specific dietary and/or exercise regimen designed to elicit low (L), normal (N), or high (H) glycogen levels in large skeletal muscle groups. Muscle glycogen concentration was determined in biopsies taken from the vastus lateralis muscle before and after each immersion. Intramuscular glycogen concentration before the immersion was significantly different among the L, N, and H trials (P less than 0.01), averaging 247 +/- 15, 406 +/- 23, and 548 +/- 42 (SE) mmol glucose units.kg dry muscle-1, respectively. The calculated metabolic heat production during the first 30 min of immersion was significantly lower during L compared with N or H (P less than 0.05). The rate at which Tre decreased was more rapid during the L immersion than either N or H (P less than 0.05), and the time during the immersion at which Tre first began to decrease also appeared sooner during L than N or H. The results suggest that low skeletal muscle glycogen levels are associated with more rapid body cooling during water immersion in humans. Higher than normal muscle glycogen levels, however, do not increase cold tolerance.

Skeletal muscle pyruvate dehydrogenase activity during maximal exercise in humans

1995 ◽  
Vol 269 (3) ◽  
pp. E458-E468 ◽  
Author(s):  
C. T. Putman ◽  
N. L. Jones ◽  
L. C. Lands ◽  
T. M. Bragg ◽  
M. G. Hollidge-Horvat ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pyruvate Dehydrogenase ◽  
Maximal Exercise ◽  
Vastus Lateralis ◽  
Active Form ◽  
Lactate Production ◽  
Glycolytic Flux ◽  
Muscle Lactate ◽  
Mitochondrial Oxidation ◽  
Exercise In Humans

The regulation of the active form of pyruvate dehydrogenase (PDHa) and related metabolic events were examined in human skeletal muscle during repeated bouts of maximum exercise. Seven subjects completed three consecutive 30-s bouts of maximum isokinetic cycling, separated by 4 min of recovery. Biopsies of the vastus lateralis were taken before and immediately after each bout. PDHa increased from 0.45 +/- 0.15 to 2.96 +/- 0.38, 1.10 +/- 0.11 to 2.91 +/- 0.11, and 1.28 +/- 0.18 to 2.82 +/- 0.32 mmol.min-1.kg wet wt-1 during bouts 1, 2, and 3, respectively. Glycolytic flux was 13-fold greater than PDHa in bouts 1 and 2 and 4-fold greater during bout 3. This discrepancy between the rate of pyruvate production and oxidation resulted in substantial lactate accumulation to 89.5 +/- 11.6 in bout 1, 130.8 +/- 13.8 in bout 2, and 106.6 +/- 10.1 mmol/kg dry wt in bout 3. These events coincided with an increase in the mitochondrial oxidation state, as reflected by a fall in mitochondrial NADH/NAD, indicating that muscle lactate production during exercise was not an O2-dependent process in our subjects. During exercise the primary factor regulating PDHa transformation was probably intracellular Ca2+. In contrast, the primary regulatory factors causing greater PDHa during recovery were lower ATP/ADP and NADH/NAD and increased concentrations of pyruvate and H+. Greater PDHa during recovery facilitated continued oxidation of the lactate load between exercise bouts.

Muscle metabolism during prolonged exercise in humans: influence of carbohydrate availability

1999 ◽  
Vol 87 (3) ◽  
pp. 1083-1086 ◽  
Author(s):  
G. McConell ◽  
R. J. Snow ◽  
J. Proietto ◽  
M. Hargreaves
Keyword(s):  
Oxygen Uptake ◽  
Vastus Lateralis ◽  
Time To Exhaustion ◽  
Endurance Capacity ◽  
Vastus Lateralis Muscle ◽  
Double Blind ◽  
Muscle Lactate ◽  
Carbohydrate Ingestion ◽  
Inosine Monophosphate ◽  
Muscle Energy

Eight endurance-trained men cycled to volitional exhaustion at 69 ± 1% peak oxygen uptake on two occasions to examine the effect of carbohydrate supplementation during exercise on muscle energy metabolism. Subjects ingested an 8% carbohydrate solution (CHO trial) or a sweet placebo (Con trial) in a double-blind, randomized order, with vastus lateralis muscle biopsies ( n = 7) obtained before and immediately after exercise. No differences in oxygen uptake, heart rate, or respiratory exchange ratio during exercise were observed between the trials. Exercise time to exhaustion was increased by ∼30% when carbohydrate was ingested [199 ± 21 vs. 152 ± 9 (SE) min, P < 0.05]. Plasma glucose and insulin levels during exercise were higher and plasma free fatty acids lower in the CHO trial. No differences between trials were observed in the decreases in muscle glycogen and phosphocreatine or the increases in muscle lactate due to exercise. Muscle ATP levels were not altered by exercise in either trial. There was a small but significant increase in muscle inosine monophosphate levels at the point of exhaustion in both trials, and despite the subjects in CHO trial cycling 47 min longer, their muscle inosine monophosphate level was significantly lower than in the Con trial (CHO: 0.16 ± 0.08, Con: 0.23 ± 0.09 mmol/kg dry muscle). These data suggest that carbohydrate ingestion may increase endurance capacity, at least in part, by improving muscle energy balance.

Muscle blood flow during exercise in sedentary and trained hypothyroid rats

1995 ◽  
Vol 269 (6) ◽  
pp. H1949-H1954 ◽  
Author(s):  
R. M. McAllister ◽  
M. D. Delp ◽  
K. A. Thayer ◽  
M. H. Laughlin
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Muscle Blood Flow ◽  
Treadmill Running ◽  
Exercise Intolerance ◽  
Vastus Lateralis Muscle ◽  
Blood Flows ◽  
Vastus Intermedius

Hypothyroidism is characterized by exercise intolerance. We hypothesized that active muscle blood flow during in vivo exercise is inadequate in the hypothyroid state. Additionally, we hypothesized that endurance exercise training would restore normal blood flow during acute exercise. To test these hypotheses, rats were made hypothyroid (Hypo) over 3-4 mo with propylthiouracil. A subset of Hypo rats was trained (THypo) on a treadmill at 30 m/min (15% grade) for 60 min/day 5 days/wk over 10-15 wk. Hypothyroidism was evidenced by approximately 80% reductions in plasma triiodothyronine levels in Hypo and THypo and by 40-50% reductions in citrate synthase activities in high oxidative muscles in Hypo compared with euthyroid (Eut) rats. Training efficacy was indicated by increased (25-100%) citrate synthase activities in muscles of THypo vs. Hypo. Regional blood flows were determined by the radiolabeled microsphere method before exercise and at 1-2 min of treadmill running at 15 m/min (0% grade). Preexercise muscle blood flows were generally similar among groups. During exercise, however, flows were lower in Hypo than in Eut for high oxidative muscles such as the red section of vastus lateralis [277 +/- 24 and 153 +/- 13 (SE) ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01] and vastus intermedius (317 +/- 32 and 187 +/- 20 ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01) muscles. Training (THypo) did not normalize these flows (168 +/- 24 and 181 +/- 24 ml.min-1.100 g-1 for red section of vastus lateralis and vastus intermedius muscles, respectively). Blood flows to low oxidative muscle, such as the white section of vastus lateralis muscle, were similar among groups (21 +/- 5, 25 +/- 4, and 34 +/- 7 ml.min-1.100 g-1 for Eut, Hypo, and THypo, respectively; P = NS). These findings indicate that hypothyroidism is associated with reduced blood flow to skeletal muscle during exercise, suggesting that impaired delivery of nutrients to and/or removal of metabolites from skeletal muscle contributes to the poor exercise tolerance characteristic of hypothyroidism.

A single bout of exercise activates matrix metalloproteinase in human skeletal muscle

2007 ◽  
Vol 102 (6) ◽  
pp. 2346-2351 ◽  
Author(s):  
E. Rullman ◽  
H. Rundqvist ◽  
D. Wågsäter ◽  
H. Fischer ◽  
P. Eriksson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Matrix Metalloproteinase ◽  
Vastus Lateralis ◽  
Tissue Expression ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Vastus Lateralis Muscle ◽  
Protein Levels ◽  
Single Bout ◽  
Exercise Induced ◽  
Muscle Biopsies

The aims of this study were 1) to characterize changes in matrix metalloproteinase (MMP), endostatin, and vascular endothelial growth factor (VEGF)-A expression in skeletal muscle in response to a single bout of exercise in humans; and 2) to determine if any exchange of endostatin and VEGF-A between circulation and the exercising leg is associated with a change in the tissue expression or plasma concentration of these factors. Ten healthy males performed 65 min of cycle exercise, and muscle biopsies were obtained from the vastus lateralis muscle at rest and immediately and 120 min after exercise. In the muscle biopsies, measurements of mRNA expression levels of MMP-2, MMP-9, MMP-14, and tissue inhibitor of metalloproteinase; VEGF and endostatin protein levels; and MMP activities were performed. Femoral arterial and venous concentrations of VEGF-A and endostatin were determined before, during, and 120 min after exercise. A single bout of exercise increased MMP-9 mRNA and activated MMP-9 protein in skeletal muscle. No measurable increase of endostatin was observed in the skeletal muscle or in plasma following exercise. A concurrent increase in skeletal muscle VEGF-A mRNA and protein levels was induced by exercise, with no signs of peripheral uptake from the circulation. However, a decrease in plasma VEGF-A concentration occurred following exercise. Thus 1) a single bout of exercise activated the MMP system without any resulting change in tissue endostatin protein levels, and 2) the increased VEGF-A protein levels are due to changes in the skeletal muscle tissue itself. Other mechanisms are responsible for the observed exercise-induced decrease in VEGF-A in plasma.

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