Endurance training, expression, and physiology of LDH, MCT1, and MCT4 in human skeletal muscle

2000 ◽  
Vol 278 (4) ◽  
pp. E571-E579 ◽  
Author(s):  
Hervé Dubouchaud ◽  
Gail E. Butterfield ◽  
Eugene E. Wolfel ◽  
Bryan C. Bergman ◽  
George A. Brooks

To evaluate the effects of endurance training on the expression of monocarboxylate transporters (MCT) in human vastus lateralis muscle, we compared the amounts of MCT1 and MCT4 in total muscle preparations (MU) and sarcolemma-enriched (SL) and mitochondria-enriched (MI) fractions before and after training. To determine if changes in muscle lactate release and oxidation were associated with training-induced changes in MCT expression, we correlated band densities in Western blots to lactate kinetics determined in vivo. Nine weeks of leg cycle endurance training [75% peak oxygen consumption (V˙o 2 peak)] increased muscle citrate synthase activity (+75%, P < 0.05) and percentage of type I myosin heavy chain (+50%, P < 0.05); percentage of MU lactate dehydrogenase-5 (M4) isozyme decreased (−12%, P < 0.05). MCT1 was detected in SL and MI fractions, and MCT4 was localized to the SL. Muscle MCT1 contents were consistent among subjects both before and after training; in contrast, MCT4 contents showed large interindividual variations. MCT1 amounts significantly increased in MU, SL, and MI after training (+90%, +60%, and +78%, respectively), whereas SL but not MU MCT4 content increased after training (+47%, P < 0.05). Mitochondrial MCT1 content was negatively correlated to net leg lactate release at rest ( r = −0.85, P < 0.02). Sarcolemmal MCT1 and MCT4 contents correlated positively to net leg lactate release at 5 min of exercise at 65%V˙o 2 peak ( r = 0.76, P < 0.03 and r = 0.86, P < 0.01, respectively). Results support the conclusions that 1) endurance training increases expression of MCT1 in muscle because of insertion of MCT1 into both sarcolemmal and mitochondrial membranes, 2) training has variable effects on sarcolemmal MCT4, and 3) both MCT1 and MCT4 participate in the cell-cell lactate shuttle, whereas MCT1 facilitates operation of the intracellular lactate shuttle.

1993 ◽  
Vol 264 (2) ◽  
pp. E215-E220 ◽  
Author(s):  
A. R. Coggan ◽  
R. J. Spina ◽  
W. M. Kohrt ◽  
J. O. Holloszy

It has been hypothesized that endurance training reduces carbohydrate utilization during exercise via citrate-mediated inhibition of phosphofructokinase (PFK). To test this hypothesis, vastus lateralis muscle biopsy samples were obtained from eight men before and immediately (approximately 10 s) after 2 h of cycle ergometer exercise at 60% of pretraining peak O2 uptake, both before and after 12 wk of endurance exercise training (3 days/wk running, 3 days/wk interval cycling). Training increased muscle citrate synthase (CS) activity from 3.69 +/- 0.48 (SE) to 5.30 +/- 0.42 mol.h-1.kg protein-1 and decreased the mean respiratory exchange ratio during exercise from 0.92 +/- 0.01 to 0.88 +/- 0.01 (both P < 0.001). Muscle citrate concentration at the end of exercise correlated significantly with CS activity (r = 0.70; P < 0.005) and was slightly but not significantly higher after training (0.80 +/- 0.19 vs. 0.54 +/- 0.19 mmol/kg dry wt; P = 0.16). Muscle glucose 6-phosphate (G-6-P) concentration at the end of exercise, however, was 31% lower in the trained state (1.17 +/- 0.10 vs. 1.66 +/- 0.27 mmol/kg dry wt; P < 0.05), in keeping with a 36% decrease in the amount of muscle glycogen utilized (133 +/- 22 vs. 209 +/- 19 mmol.kg dry wt-1.2 h-1; P < 0.01). The lower G-6-P concentration after training suggests that the training-induced reduction in carbohydrate utilization results from attenuation of flux before the PFK step in glycolysis and is not due to citrate-mediated inhibition of PFK.


2005 ◽  
Vol 98 (1) ◽  
pp. 186-192 ◽  
Author(s):  
R. J. Aughey ◽  
C. J. Gore ◽  
A. G. Hahn ◽  
A. P. Garnham ◽  
S. A. Clark ◽  
...  

Athletes commonly attempt to enhance performance by training in normoxia but sleeping in hypoxia [live high and train low (LHTL)]. However, chronic hypoxia reduces muscle Na+-K+-ATPase content, whereas fatiguing contractions reduce Na+-K+-ATPase activity, which each may impair performance. We examined whether LHTL and intense exercise would decrease muscle Na+-K+-ATPase activity and whether these effects would be additive and sufficient to impair performance or plasma K+ regulation. Thirteen subjects were randomly assigned to two fitness-matched groups, LHTL ( n = 6) or control (Con, n = 7). LHTL slept at simulated moderate altitude (3,000 m, inspired O2 fraction = 15.48%) for 23 nights and lived and trained by day under normoxic conditions in Canberra (altitude ∼600 m). Con lived, trained, and slept in normoxia. A standardized incremental exercise test was conducted before and after LHTL. A vastus lateralis muscle biopsy was taken at rest and after exercise, before and after LHTL or Con, and analyzed for maximal Na+-K+-ATPase activity [K+-stimulated 3- O-methylfluorescein phosphatase (3- O-MFPase)] and Na+-K+-ATPase content ([3H]ouabain binding sites). 3- O-MFPase activity was decreased by −2.9 ± 2.6% in LHTL ( P < 0.05) and was depressed immediately after exercise ( P < 0.05) similarly in Con and LHTL (−13.0 ± 3.2 and −11.8 ± 1.5%, respectively). Plasma K+ concentration during exercise was unchanged by LHTL; [3H]ouabain binding was unchanged with LHTL or exercise. Peak oxygen consumption was reduced in LHTL ( P < 0.05) but not in Con, whereas exercise work was unchanged in either group. Thus LHTL had a minor effect on, and incremental exercise reduced, Na+-K+-ATPase activity. However, the small LHTL-induced depression of 3- O-MFPase activity was insufficient to adversely affect either K+ regulation or total work performed.


1984 ◽  
Vol 32 (11) ◽  
pp. 1211-1216 ◽  
Author(s):  
P M Nemeth ◽  
O H Lowry

An attempt was made to determine the relationship of myoglobin content to specific fiber types in human muscle. Biopsies were obtained from biceps brachii, vastus lateralis, and gastrocnemius muscles of untrained subjects and from the vastus lateralis muscle of a highly trained athlete at peak training and at intervals of no training (detraining). Individual muscle fibers were assayed, by quantitative microanalytical methods, for myoglobin, lactate dehydrogenase, malate dehydrogenase, citrate synthase, beta-hydroxyacyl-coenzyme A dehydrogenase, and adenylokinase activities all on the same fiber. The enzyme levels were used to classify the fibers into type I or II. The results show that the content of myoglobin in human muscle does not differ greatly between fiber types in contrast to other species. The type II fibers contained, on the average, at least two-thirds as much myoglobin as type I fibers. The concentration of myoglobin did not change in either fiber type during detraining (84 days), despite marked changes in lactate dehydrogenase, adenylokinase and the three oxidative enzymes.


1998 ◽  
Vol 23 (1) ◽  
pp. 74-86 ◽  
Author(s):  
Philip D. Chilibeck ◽  
Gordon J. Bell ◽  
Teresa Socha ◽  
Tom Martin

We evaluated the effect of endurance training (cycling 3 times per week for 12 weeks) on succinate dehydrogenase (SDH) activity in the subsarcolemmal (SS) and intermyofibrillar (IMF) regions of vastus lateralis muscle fibres in 7 individuals (4 females and 3 males). SDH activity of the SS region increased 9.4% and 12.8% in type I and II fibres, respectively (p < .05). SDH activity of the IMF region increased 4.7% and 6.7% in type I and II fibres, respectively (p < .05). This was less than the increase in the SS region (p < .O5). No significant changes were observed in a control group (4 females and 3 males). These data suggest that mitochondria in the SS and IMF regions of human vastus lateralis muscle fibres are sensitive to endurance training. The greater response in the SS region suggests that the metabolic requirements of SS mitochondria were stressed to a greater extent than IMF mitochondria with endurance training. Key words: subsarcolemmal mitochondria, intermyofibrillar mitochondria


2000 ◽  
Vol 89 (3) ◽  
pp. 1033-1038 ◽  
Author(s):  
U. Frandsen ◽  
L. Höffner ◽  
A. Betak ◽  
B. Saltin ◽  
J. Bangsbo ◽  
...  

The effect of endurance training on neuronal nitric oxide synthase (nNOS) content and distribution in muscle was investigated. Seven male subjects performed 6 wk of one-legged knee-extensor endurance training ( protocol A). Muscle biopsies, obtained from vastus lateralis muscle in the untrained and the trained leg, were analyzed for nNOS protein and activity as well as immunohistochemical distribution of nNOS and endothelial nitric oxide synthase (eNOS). Muscle biopsies were also obtained from another seven male subjects before and after 6 wk of training by endurance running (p rotocol B) and analyzed for nNOS protein. No difference was found in the amount of nNOS protein in the untrained and the trained muscle either with protocol Aor protocol B ( P > 0.05). In protocol A, the activity of nNOS was 4.76 ± 0.56 pmol · mg protein−1 · min−1 in the control leg, and the level was not different in the trained leg ( P> 0.05). nNOS was present in the sarcolemma and cytosol of type I and type II muscle fibers, and the qualitative distribution was similar in untrained and trained muscle. The number of eNOS immunoreactive structures and the number of capillaries per muscle fiber were higher ( P < 0.05) after training than before. The present findings demonstrate that, in contrast to findings on animals, nNOS levels remain unaltered with endurance training in humans. Evidence is also provided that endurance training may increase the amount of eNOS, in parallel with an increase in capillaries in human muscle.


2010 ◽  
Vol 35 (5) ◽  
pp. 657-670 ◽  
Author(s):  
Howard J. Green ◽  
Aziz Batada ◽  
Bill Cole ◽  
Margaret E. Burnett ◽  
Helen Kollias ◽  
...  

We hypothesized that a season of ice hockey would result in extensive remodeling of muscle. Tissue sampled from the vastus lateralis of 15 players (age = 20.6 ± 0.4 years; mean ± SE) prior to (PRE) and following (POST) a season was used to characterize specific adaptations. Measurement of representative metabolic pathway enzymes indicated higher maximal activities in POST than in PRE (p < 0.05) for succinic dehydrogenase (3.26 ± 0.31 vs. 3.91 ± 0.11 mol·mg protein–1·min–1), citrate synthase (7.26 ± 0.70 vs. 8.70 ± 0.55 mol·mg protein–1·min–1), and phosphofructokinase (12.8 ± 1.3 vs. 14.4 ± 0.96 mol·mg protein–1·min–1) only. The season resulted in an increase in Na+-K+-ATPase concentration (253 ± 6.3 vs. 265 ± 6.0 pmol·g–1 wet weight), a decrease (p < 0.05) in maximal activity of the sarcoplasmic reticulum Ca2+-ATPase (107 ± 4.2 µmol·g protein–1·min–1 vs. 92.0 ± 4.6 µmol·g protein–1·min–1), and no change in the distribution (%) of fibre types. A smaller (p < 0.05) cross-sectional area (CSA) for both type I (–11.7%) and type IIA (–18.2%) fibres and a higher (p < 0.05) capillary count/CSA for type I (+17.9%) and type IIA (+17.2%) were also found over the season. No changes were found in peak oxygen consumption (51.4 ± 1.2 mL·kg–1·min–1 vs. 52.3 ± 1.3 mL·kg–1·min–1). The results suggest, based on the alterations in oxidative and perfusion potentials and muscle mass, that the dominant adaptations are in support of oxidative metabolism, which occurs at the expense of fibre CSA and possibly force-generating potential.


1992 ◽  
Vol 73 (6) ◽  
pp. 2517-2523 ◽  
Author(s):  
G. Grimby ◽  
A. Aniansson ◽  
M. Hedberg ◽  
G. B. Henning ◽  
U. Grangard ◽  
...  

Nine men, 78–84 yr of age, participated in a dynamometer training program 2–3 times/wk, totaling 25 sessions, using voluntary maximal isometric, concentric, and eccentric right knee–extension actions (30 and 180 degrees/s). Measurements of muscle strength with a Kin-Com dynamometer and simultaneous electromyograms (EMG) were performed of both sides before and after the training period. Muscle biopsies were taken from the right vastus lateralis muscle. The total quadriceps cross-sectional area was measured with computerized tomography. Training led to an increase in maximal torque for concentric (10% at 30 degrees/s) and eccentric (13–19%) actions in the trained leg. The EMG activity increased at maximal eccentric activities. The total cross-sectional quadriceps area of the trained leg increased by 3%, but no changes were recorded in muscle fiber areas in these subjects, who already had large mean fiber areas (5.15 microns 2 x 10(3)). The fatigue index measured from 50 consecutive concentric contractions at 180 degrees/s decreased and the citrate synthase activity increased in all but one subject. The results demonstrate that increased neural activation accompanies an increase in muscle strength at least during eccentric action in already rather active elderly men and that muscle endurance may also be improved with training.


2014 ◽  
Vol 307 (9) ◽  
pp. R1101-R1114 ◽  
Author(s):  
Jerzy A. Zoladz ◽  
Bruno Grassi ◽  
Joanna Majerczak ◽  
Zbigniew Szkutnik ◽  
Michal Korostyński ◽  
...  

The effect of prolonged endurance training on the pulmonary V̇o2 on- and off-kinetics in humans, in relation to muscle mitochondria biogenesis, is investigated. Eleven untrained physically active men (means ± SD: age 22.4 ± 1.5 years, V̇o2peak 3,187 ± 479 ml/min) performed endurance cycling training (4 sessions per week) lasting 20 wk. Training shortened τp of the pulmonary V̇o2 on-kinetics during moderate-intensity cycling by ∼19% from 28.3 ± 5.2 to 23.0 ± 4.0 s ( P = 0.005). τp of the pulmonary V̇o2 off-kinetics decreased by ∼11% from 33.7 ± 7.2 to 30.0 ± 6.6 ( P = 0.02). Training increased (in vastus lateralis muscle) mitochondrial DNA copy number in relation to nuclear DNA (mtDNA/nDNA) (+53%) ( P = 0.014), maximal citrate synthase (CS) activity (+38%), and CS protein content (+38%) ( P = 0.004), whereas maximal cytochrome c oxidase (COX) activity after training tended to be only slightly (+5%) elevated ( P = 0.08). By applying to the experimental data, our computer model of oxidative phosphorylation (OXPHOS) and using metabolic control analysis, we argue that COX activity is a much better measure of OXPHOS intensity than CS activity. According to the model, in the present study a training-induced increase in OXPHOS activity accounted for about 0–10% of the decrease in τp of muscle and pulmonary V̇o2 for the on-transient, whereas the remaining 90–100% is caused by an increase in each-step parallel activation of OXPHOS.


1999 ◽  
Vol 277 (3) ◽  
pp. R856-R862 ◽  
Author(s):  
J. Hollander ◽  
R. Fiebig ◽  
M. Gore ◽  
J. Bejma ◽  
T. Ookawara ◽  
...  

The effects of endurance training on the enzyme activity, protein content, and mRNA abundance of Mn and CuZn superoxide dismutase (SOD) were studied in various phenotypes of rat skeletal muscle. Female Sprague-Dawley rats were randomly divided into trained (T, n = 8) and untrained (U, n = 8) groups. Training, consisting of treadmill running at 27 m/min and 12% grade for 2 h/day, 5 days/wk for 10 wk, significantly increased citrate synthase activity ( P < 0.01) in the type I (soleus), type IIa (deep vastus lateralis, DVL), and mixed type II (plantaris) muscles but not in type IIb (superficial vastus lateralis, SVL) muscle. Mitochondrial (Mn) SOD activity was elevated by 80% ( P < 0.05) with training in DVL. SVL and plantaris muscle in T rats showed 54 and 42% higher pooled immunoreactive Mn SOD protein content, respectively, than those in U rats. However, no change in Mn SOD mRNA level was found in any of the muscles. CuZn SOD activity, protein content, and mRNA level in general were not affected by training, except for a 160% increase in pooled CuZn SOD protein in SVL. Training also significantly increased glutathione peroxidase and catalase activities ( P < 0.05), but only in DVL muscle. These data indicate that training adaptations of Mn SOD and other antioxidant enzymes occur primarily in type IIa fibers, probably as a result of enhanced free radical generation and modest antioxidant capacity. Differential training responses of mRNA, enzyme protein, and activity suggest that separate cellular signals may control pre- and posttranslational regulation of SOD.


1995 ◽  
Vol 78 (5) ◽  
pp. 1733-1739 ◽  
Author(s):  
V. R. Edgerton ◽  
M. Y. Zhou ◽  
Y. Ohira ◽  
H. Klitgaard ◽  
B. Jiang ◽  
...  

Biopsies from the vastus lateralis muscle were obtained from three astronauts before and after two 5-day flights and from five astronauts before and after one 11-day flight (space shuttle flights: STS-32, -33, and -34). Muscle fibers from two separate samples from each biopsy were classified as type I and II or as type I, IIA, and IIB by using qualitative myofibrillar adenosinetriphosphatase (ATPase) staining. Cross-sectional area (CSA), number of capillaries per fiber, and the activities of succinate dehydrogenase (SDH), alpha-glycerophosphate dehydrogenase (GPD), and myofibrillar ATPase were determined from one sample of fibers of each myofibrillar ATPase type. Postflight biopsies had 6–8% fewer type I fibers than preflight. Mean fiber CSAs were 16–36% smaller after the 11-day flight with the relative effect being type IIB > IIA > I. Mean fiber CSAs were 11 and 24% smaller in type I and II fibers after 5 days of flight. Myofibrillar ATPase activities increased in type II but not in type I fibers after flight, whereas SDH activity was unaffected in either fast or slow fibers. GPD activity in type I fibers was approximately 80% higher (P > 0.05) postflight compared with preflight. Myofibrillar ATPase/SDH ratios in type II fibers were higher after than before flight, suggesting that some fast fibers were more susceptible to fatigue after flight. The GPD/SDH ratios were elevated in some type I fibers after spaceflight. The number of capillaries per fiber was 24% lower after than before flight, whereas the number of capillaries per unit CSA of muscle tissue was unchanged. These data suggest that adaptations in the size, metabolic properties, and vascularity of muscle fibers can occur rapidly in the space environment. These adaptations were qualitatively similar to those observed in animals after actual or simulated spaceflight conditions for short periods.


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