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  • 1.
    Mascher, Henrik
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Intracellular signaling in human skeletal muscle following different modes of exercise2010Doctoral 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.

  • 2.
    Mascher, Henrik
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Andersson, H
    Nilsson, P-A
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Changes in signalling pathways regulating protein synthesis in human muscle in the recovery period after endurance exercise.2007In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 191, no 1, p. 67-75Article in journal (Refereed)
    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.

  • 3.
    Mascher, Henrik
    et al.
    Swedish School of Sport and Health Sciences, GIH.
    Apró, William
    Swedish School of Sport and Health Sciences, GIH.
    Pontén, Marjan
    Swedish School of Sport and Health Sciences, GIH.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH.
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH.
    Effects of essential amino acid supplementation on markers for anabolic and catabolic response to resistance exercise in female subjects2010Conference paper (Other academic)
  • 4.
    Mascher, Henrik
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Rooyackers, Olav
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Enhanced rates of muscle protein synthesis and elevated mTOR signalling following endurance exercise in human subjects.2011In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 202, no 2, p. 175-84Article in journal (Refereed)
    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.

  • 5.
    Mascher, Henrik
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Tannerstedt, Jörgen
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Nya aspekter på aminosyrors roll i den muskulära anpassningen till träning2006In: Svensk Idrottsforskning: Organ för Centrum för Idrottsforskning, ISSN 1103-4629, Vol. 15, no 3, p. 56-60Article in journal (Other academic)
    Abstract [sv]

    Sammanfattningsvis kan sägas att tillgängligheten av protein/aminosyror är nödvändig för den muskulära anpassningen till träning vid både styrke- och uthållighetsträning. Betydligt fler studier har undersökt effekterna på styrketräning, men vid båda typer av träning är dock kunskaperna om de bakomliggande mekanismerna ännu så länge små. Genom den omfattande forskning som pågår inom området kommer med all säkerhet de molekylära och cellulära förändringar som sker i samband med träning att kartläggas inom en relativt snar framtid. Därmed öppnas nya möjligheter att förbättra och optimera träningen, t.ex. genom kombination av olika typer av aktiviteter (uthållighet och styrketräning). Denna kunskap är också avgörande för att förstå och eventuellt kunna påverka träningseffekten genom förändringar i nutritionens sammansättning.

  • 6.
    Mascher, Henrik
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Tannerstedt, Jörgen
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Brink-Elfegoun, Thibault
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Ekblom, Björn
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Björn Ekblom's research group.
    Gustafsson, Thomas
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Repeated resistance exercise training induces different changes in mRNA expression of MAFbx and MuRF-1 in human skeletal muscle.2008In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 294, no 1, p. E43-51Article in journal (Refereed)
    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.

  • 7. Terzis, Gerasimos
    et al.
    Georgiadis, Giorgos
    Stratakos, Grigoris
    Vogiatzis, Ioannis
    Kavouras, Stavros
    Manta, Panagiota
    Mascher, Henrik
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Resistance exercise-induced increase in muscle mass correlates with p70S6 kinase phosphorylation in human subjects.2008In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 102, no 2, p. 145-52Article in journal (Refereed)
    Abstract [en]

    The purpose of the present study was to investigate the possible relationship between a change in Thr(389) phosphorylation of p70S6 kinase (p70(S6k)) after a single resistance training session and an increase in skeletal muscle mass following short-term resistance training. Eight male subjects performed an initial resistance training session in leg press, six sets of 6RM with 2 min between sets. Muscle biopsies were obtained from the vastus lateralis before (T1) and 30 min after the initial training session (T2). Six of these subjects completed a 14-week resistance-training programme, three times per week (nine exercises, six sets, 6RM). A third muscle biopsy was obtained at the end of the 14-week training period (T3). One repetition maximum (1RM) squat, bench press and leg press strength as well as fat-free mass (FFM, with dual energy X-ray absorptiometry) were determined at T1 and T3. The results show that the increase in Thr(389) phosphorylation of p70(S6k) after the initial training session was closely correlated with the percentage increase in whole body FFM (r = 0.89, P < 0.01), FFM(leg) (r = 0.81, P < 0.05), 1RM squat (r = 0.84, P < 0.05), and type IIA muscle fibre cross sectional area (r = 0.82, P < 0.05) after 14 weeks of resistance training. These results may suggest that p70(S6k) phosphorylation is involved in the signalling events leading to an increase in protein accretion in human skeletal muscle following resistance training, at least during the initial training period.

  • 8. Terzis, Gerasimos
    et al.
    Spengos, Konstantinos
    Mascher, Henrik
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Georgiadis, Giorgos
    Manta, Panagiota
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    The degree of p70(S6k) and S6 phosphorylation in human skeletal muscle in response to resistance exercise depends on the training volume.2010In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 110, no 4, p. 835-43Article in journal (Refereed)
    Abstract [en]

    Regular performance of resistance exercise induces an increase in skeletal muscle mass, however, the molecular mechanisms underlying this effect are not yet fully understood. The purpose of the present investigation was to examine acute changes in molecular signalling in response to resistance exercise involving different training volumes. Eight untrained male subjects carried out one, three and five sets of 6 repetition maximum (RM) in leg press exercise in a random order. Muscle biopsies were taken from the vastus lateralis both prior to and 30 min after each training session and the effect on protein signalling was studied. Phosphorylation of Akt was not altered significantly after any of the training protocols, whereas that of the mammalian target of rapamycin was enhanced to a similar extent by training at all three volumes. The phosphorylation of p70S6 kinase (p70(S6k)) was elevated threefold after 3 × 6 RM and sixfold after 5 × 6 RM, while the phosphorylation of S6 was increased 30- and 55-fold following the 3 × 6 RM and 5 × 6 RM exercises, respectively. Moreover, the level of the phosphorylated form of the gamma isoform of p38 MAPK was enhanced three to fourfold following each of the three protocols, whereas phosphorylation of ERK1/2 was unchanged 30 min following exercise. These findings indicate that when exercise is performed in a fasted state, the increase in phosphorylation of signalling molecules such as p70(S6k) and the S6 ribosomal protein in human muscle depends on the exercise volume.

  • 9. Wang, Li
    et al.
    Mascher, Henrik
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Psilander, Niklas
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Resistance exercise enhances the effect of endurance training on molecular signaling in human skeletal muscleManuscript (preprint) (Other academic)
  • 10. Wang, Li
    et al.
    Psilander, Niklas
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Eva Blomstrand's research group.
    Mascher, Henrik
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Sahlin, Kent
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Research group for Mitokondriell funktion och metabolisk kontroll.
    Resistance exercise enhances the molecular signaling of mitochondrial biogenesis induced by endurance exercise in human skeletal muscle.2011In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 111, no 5, p. 1335-1344Article in journal (Refereed)
    Abstract [en]

    Combining endurance and strength training (concurrent training) may change the adaptation compared with single mode training. However, the site of interaction and the mechanisms are unclear. We have investigated the hypothesis that molecular signaling of mitochondrial biogenesis after endurance exercise is impaired by resistance exercise. Ten healthy subjects performed either only endurance exercise (E: 1h cycling at ~65% of VO(2max)) or endurance exercise followed by resistance exercise (ER: 1h cycling + 6 sets of leg press at 70-80% of 1 repetition maximum) in a randomized cross-over design. Muscle biopsies were obtained before and after exercise (1 and 3h Post cycling). The mRNA of genes related to mitochondrial biogenesis (PGC-1α, PRC) and substrate regulation (PDK4) increased after both E and ER, but the mRNA levels were about 2-fold higher after ER (P<0.01). Phosphorylation of proteins involved in the signaling cascade of protein synthesis (mTOR, S6K1 and eEF2) was altered after ER but not after E. Moreover, ER induced a larger increase in mRNA of genes associated with positive mTOR signaling (cMyc and Rheb). Phosphorylation of AMPK, ACC and Akt increased similarly at 1h Post (P<0.01) after both types of exercise. Contrary to our hypothesis, the results demonstrate that resistance exercise, performed after endurance exercise, amplifies the adaptive signaling response of mitochondrial biogenesis compared with single-mode endurance exercise. The mechanism may relate to a crosstalk between signaling pathways mediated by mTOR. The results suggest that concurrent training may be beneficial for the adaptation of muscle oxidative capacity.

  • 11. Ydfors, Mia
    et al.
    Fischer, Helene
    Mascher, Henrik
    Blomstrand, Eva
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Eva Blomstrand's research group.
    Norrbom, Jessica
    Gustafsson, Thomas
    The truncated splice variants, NT-PGC-1alpha and PGC-1alpha4, increase with both endurance and resistance exercise in human skeletal muscle2013In: Physiological Reports, ISSN 2051-817X, Vol. 1, no 6, p. e00140 Page 1-e00140 Page 9Article in journal (Refereed)
    Abstract [en]

    Recently, a truncated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) splice variant, PGC-1α4, that originates from the alternative promoter was shown to be induced by resistance exercise and to elicit muscle hypertrophy without coactivation of “classical” PGC-1α targets involved in mitochondrial biogenesis and angiogenesis. In order to test if distinct physiological adaptations are characterized by divergent induction of PGC-1α splice variants, we investigated the expression of truncated and nontruncated PGC-1α splice variants and PGC-1α transcripts originating from the alternative and the proximal promoter, in human skeletal muscle in response to endurance and resistance exercise. Both total PGC-1α and truncated PGC-1α mRNA expression were increased 2 h after endurance (P < 0.01) and resistance exercise (P < 0.01), with greater increases after endurance exercise (P < 0.05). Expression of nontruncated PGC-1α increased significantly in both exercise groups (P < 0.01 for both groups) without any significant differences between the groups. Both endurance and resistance exercise induced truncated as well as nontruncated PGC-1α transcripts from both the alternative and the proximal promoter. Further challenging the hypothesis that induction of distinct PGC-1α splice variants controls exercise adaptation, both nontruncated and truncated PGC-1α transcripts were induced in AICAR-treated human myotubes (P < 0.05). Thus, contrary to our hypothesis, resistance exercise did not specifically induce the truncated forms of PGC-1α. Induction of truncated PGC-1α splice variants does not appear to underlie distinct adaptations to resistance versus endurance exercise. Further studies on the existence of numerous splice variants originating from different promoters are needed.

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