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Intracellular signaling in human skeletal muscle following different modes of exercise
Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences. (Karolinska institutet)
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Resistance and endurance exercise when performed regularly will cause specific adaptations in human skeletal muscle. Resistance exercise is known to increase strength and muscle mass while endurance training increases vascularisation and mitochondrial density which results in enhanced oxidative capacity. To understand how these adaptations occur, it is important to examine the molecular signaling events in muscle. The Akt-mTOR pathway has been shown to have an important function in the stimulation of protein synthesis. This pathway is stimulated following resistance exercise in human muscle. During the work included in this thesis it has become clear that endurance exercise also stimulates Akt-mTOR signaling in human skeletal muscle. Study (I) revealed an increased phosphorylation of mTOR, Akt and GSK3 and a marked decrease in eEF2 phosphorylation indicating a stimulatory response on elongation and initiation of protein synthesis in the early recovery phase. Furthermore, as shown in study (II), this stimulatory response is followed by an increase in the fractional synthetic rate (FSR), which was progressively increased when measured up to 3 h following endurance exercise. It is usually recommended that resistance exercise is performed 2-3 times per week. In study (III), markers for anabolic (Akt, mTOR, p70S6k, rpS6, eEF2 and GSK-3β) as well as catabolic (MAFbx and MuRF-1) processes were investigated following two sessions of resistance exercise separated by 48 hours. From this study it appears that anabolic signaling is slightly enhanced following the second exercise session, and furthermore, the changes in gene expression related to muscle protein degradation (MAFbx and MuRF-1) is attenuated during the second exercise session. Endurance exercise can compromise the adaptive response of strength training. On the other hand, there is some evidence suggesting that combining endurance training with resistance exercise may have beneficial effects on endurance exercise performance. The final study was designed to evaluate whether resistance exercise can enhance the muscle adaptive response to endurance exercise with respect to molecular signaling related to increased protein synthesis and specific markers for mitochondrial biogenesis. An enhanced signaling response was actually found in the combined exercise protocol. Specifically, expression of genes related to increased mitochondrial biogenesis and oxidative metabolism (PGC-1α, PRC and PDK-4 mRNA) as well markers for anabolic signaling (mTOR, p70S6k), was enhanced when endurance exercise was followed by a session of heavy resistance exercise. This data support the notion that including resistance exercise in endurance training may be beneficial. In summary, mixed muscle FSR is gradually increased following endurance exercise when measured during the first 3 h of recovery and this increase is accompanied by stimulation of mTOR signaling. Resistance exercise enhances effects on anabolic signaling and attenuates expression of genes involved in muscle protein breakdown and inhibition of muscle growth during a second exercise session performed two days after the first. Finally, combining endurance and heavy resistance exercise can enhance acute adaptive responses and indicates that combined exercise may be superior to endurance exercise alone.

Place, publisher, year, edition, pages
Stockholm: Karolinska institutet , 2010.
National Category
Medical and Health Sciences
Research subject
Medicine/Technology
Identifiers
URN: urn:nbn:se:gih:diva-2459ISBN: 978-91-7457-144-8 (print)OAI: oai:DiVA.org:gih-2459DiVA: diva2:563987
Public defence
2010-12-03, Aulan, GIH, Lidingövägen 1, Stockholm, 09:00
Opponent
Supervisors
Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2012-12-18Bibliographically approved
List of papers
1. Changes in signalling pathways regulating protein synthesis in human muscle in the recovery period after endurance exercise.
Open this publication in new window or tab >>Changes in signalling pathways regulating protein synthesis in human muscle in the recovery period after endurance exercise.
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2007 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 191, no 1, 67-75 p.Article in journal (Refereed) Published
Abstract [en]

AIM: Exercise induced alterations in the rate of muscle protein synthesis may be related to activity changes in signalling pathways involved in protein synthesis. The aim of the present study was to investigate whether such changes in enzyme phosphorylation occur after endurance exercise. METHODS: Six male subjects performed ergometer cycling exercise for 1 h at 75% of the maximal oxygen uptake. Muscle biopsy samples from the vastus lateralis were taken before, immediately after, 30 min, 1 h, 2 h and 3 h after exercise for the determination of protein kinase B (PKB/Akt), mammalian target of rapamycin (mTOR), glycogen synthase 3 kinase (GSK-3), p70S6 kinase (p70(S6k)) and eukaryotic elongation factor 2 (eEF2) phosphorylation. RESULTS: The phosphorylation of Akt was unchanged directly after exercise, but two- to fourfold increased 1 and 2 h after the exercise, whereas GSK-3alpha and beta phosphorylation were two- to fourfold elevated throughout most of the 3-h recovery period. Phosphorylation of mTOR was elevated threefold directly after, 30 min and 2 h after exercise and eEF2 phosphorylation was decreased by 35-75% from 30 min to 3 h-recovery. Exercise led to a five- to eightfold increase in Ser(424)/Thr(421) phosphorylation of p70(S6k) up to 30 min after exercise, but no change in Thr(389) phosphorylation. CONCLUSIONS: The marked decrease in eEF2 phosphorylation suggests an activation of translation elongation and possibly protein synthesis in the recovery period after sustained endurance exercise. The lack of p70(S6k) activation suggests that translation initiation is activated via alternative pathways, possibly via the activation of eukaryotic initiating factor 2B.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:gih:diva-958 (URN)10.1111/j.1748-1716.2007.01712.x (DOI)17488244 (PubMedID)
Available from: 2009-09-24 Created: 2009-09-21 Last updated: 2017-12-13Bibliographically approved
2. Enhanced rates of muscle protein synthesis and elevated mTOR signalling following endurance exercise in human subjects.
Open this publication in new window or tab >>Enhanced rates of muscle protein synthesis and elevated mTOR signalling following endurance exercise in human subjects.
2011 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 202, no 2, 175-84 p.Article in journal (Refereed) Published
Abstract [en]

AIM: The major aim of this study was to determine the fractional rate of protein synthesis (FSR) during the early period of recovery after intensive aerobic exercise in the absence of nutritional supplementation.

METHODS: Sixteen male subjects performed one-legged cycling exercise for 1 h at approx. 65-70% of their one-legged maximal oxygen uptake. Using the stable isotope technique, the FSR in the vastus lateralis of both legs were determined during two periods, 0-90 min (n = 8) and 90-180 min (n = 8) after exercise. Biopsies were taken from both exercising and resting muscle before exercise, immediately after and following 90 or 180 min of recovery.

RESULTS: During the initial 90 min of recovery, FSR in the exercising muscle tended to be higher than in the resting muscle (1.57 ± 0.12 vs. 1.44 ± 0.07% 24 h(-1); P = 0.1) and was significantly higher during the period 90-180 min after exercise (1.74 ± 0.14 vs. 1.43 ± 0.12% 24 h(-1) ; P < 0.05). Exercise induced a 60% increase (P < 0.05) in phosphorylation of mTOR and a fivefold increase (P < 0.05) in Thr(389) phosphorylation of p70S6 kinase as well as a 30% reduction (P < 0.05) in phosphorylation of eEF2. Phosphorylation of AMP-activated protein kinase was enhanced by 40% (P < 0.05) after exercise, but no significant effect on phosphorylation of Akt, or eIF2Bε was observed immediately after exercise.

CONCLUSION: These findings indicate that during the first 3 h of recovery after intensive endurance exercise FSR gradually increases. Moreover, a stimulation of the mTOR-signalling pathway may be at least partially responsible for this elevated protein synthesis.

National Category
Medical and Health Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-1916 (URN)10.1111/j.1748-1716.2011.02274.x (DOI)21385328 (PubMedID)
Note

At the time of Henrik Mascher's dissertation the article was submitted.

Available from: 2011-10-14 Created: 2011-10-14 Last updated: 2017-12-08Bibliographically approved
3. Repeated resistance exercise training induces different changes in mRNA expression of MAFbx and MuRF-1 in human skeletal muscle.
Open this publication in new window or tab >>Repeated resistance exercise training induces different changes in mRNA expression of MAFbx and MuRF-1 in human skeletal muscle.
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2008 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 294, no 1, E43-51 p.Article in journal (Refereed) Published
Abstract [en]

The gain in muscle mass as a result of resistance training is dependent on changes in both anabolic and catabolic reactions. A frequency of two to three exercise sessions per week is considered optimal for muscle gain in untrained individuals. Our hypothesis was that a second exercise session would enlarge the anabolic response and/or decrease the catabolic response. Eight male subjects performed resistance exercise on two occasions separated by 2 days. Muscle biopsies were taken from the vastus lateralis before and 15 min, 1 h, and 2 h after exercise. Exercise led to severalfold increases in phosphorylation of mTOR at Ser2448, p70 S6 kinase (p70S6k) at Ser424/Thr421 and Thr389, and ribosomal protein S6, which persisted for up to 2 h of recovery on both occasions. There was a tendency toward a larger effect of the second exercise on p70S6k and S6, but the difference did not reach statistical significance. The mRNA expression of MuRF-1, which increased after exercise, was 30% lower after the second exercise session than after the first one. MAFbx expression was not altered after exercise but downregulated 30% 48 h later, whereas myostatin expression was reduced by 45% after the first exercise and remained low until after the second exercise session. The results indicate that 1) changes in expression of genes involved in protein degradation are attenuated as a response to repetitive resistance training with minor additional increases in enzymes regulating protein synthesis and 2) the two ubiquitin ligases, MuRF-1 and MAFbx, are differently affected by the exercise as well as by repeated exercise.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:gih:diva-960 (URN)10.1152/ajpendo.00504.2007 (DOI)17971512 (PubMedID)
Available from: 2009-09-24 Created: 2009-09-21 Last updated: 2017-12-13Bibliographically approved
4. Resistance exercise enhances the effect of endurance training on molecular signaling in human skeletal muscle
Open this publication in new window or tab >>Resistance exercise enhances the effect of endurance training on molecular signaling in human skeletal muscle
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(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-2460 (URN)
Note

At the time of Henrik Mascher's dissertation the publication was a manuscript.

Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2012-11-01Bibliographically approved

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