Abstract
We tested the hypothesis that strength exercise after intermittent aerobic exercise might activate signaling pathways that regulate mitochondrial biogenesis (activation of the AMPK and p38 pathways; the expression of PGC-1α, NT-PGC-1α, TFAM, and VEGFA mRNA), protein synthesis (phosphorylation level of p70S6K1Thr389 and eEF2Thr56; the expression IGF-1Ea, IGF-1Ec (MGF), and REDD1 mRNA) and proteolysis (phosphorylation level of FOXO1Ser256; the expression of MURF1, MAFbx, and Myostatin mRNA) in trained skeletal muscles. Nine amateur endurance-trained athletes performed an intermittent aerobic cycling (70 min), followed by one-leg strength exercise (ES: four sets of knee extensions till exhaustion), while the other leg was resting (E). Gene expression and protein level were evaluated in samples from m. vastus lateralis taken before the exercise, 40 min, 5 and 22 h after the aerobic exercise. The phosphorylation level of the АССSer79/222 (an endogenous marker of AMPK activity) and the expression of PGC-1α-related gene TFAM (a marker of mitochondrial biogenesis) were increased after E exercise and did not changed after ES exercise. The expression of PGC-1α and truncated isoform NT-PGC-1α was increased in both legs as well. Insulin concentration in blood was decreased significantly (7.5-fold) after aerobic exercise; the phosphorylation level of FOXOSer256 (a regulator of ubiquitin-related proteolysis) was decreased in both legs, which means that it was activated in both types of exercises; at the same time, the expression of the E3-ubiquitin ligase gene MURF1, its target, was only increased after E exercise. Neither aerobic or combined exercise had a significant effect on the regulation of protein synthesis: there were no changes in either expression of IGF-1Ea and IGF-1Ec(MGF) mRNA isoforms or the phosphorylation levels of markers of protein synthesis p70S6K1Thr389 and eEF2Thr56. Thus, the performance of strength exercise immediately after aerobic one prevented the activation of mitochondrial biogenesis in endurance-trained muscles: activation of AMPK pathway and the expression of TFAM are decreased, while protein synthesis regulation is not affected. At the same time, the strength exercise inhibited the expression of MURF1 gene (a marker of ubiquitin proteasome system), which was induced by aerobic exercise. We suggest that strength exercise performed immediately after intense intermittent aerobic exercise may have a negative effect on aerobic performance if used chronically.
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References
Olesen, J., Kiilerich, K., and Pilegaard, H., PGC-1alpha- mediated adaptations in skeletal muscle, Pflügers Arch., 2010, vol. 460, no. 1, p. 153.
Kohn, T.A., Essén-Gustavsson, B., and Myburgh, K.H., Specific muscle adaptations in type II fibers after high-intensity interval training of welltrained runners, Scand. J. Med. Sci. Sports, 2011, vol. 21, no. 6, p. 765.
Kraemer, W.J., Patton, J.F., Gordon, S.E., et al., Compatibility of high-intensity strength and endurance training on hormonal and skeletal muscle adaptations, J. Appl. Physiol., 1995, vol. 78, no. 3, p. 976.
Pikosky, M.A., Gaine, P.C., Martin, W.F., et al., Aerobic exercise training increases skeletal muscle protein turnover in healthy adults at rest, J. Nutr., 2006, vol. 136, no. 2, p. 379.
Atherton, P.J., Babraj, J., Smith, K., et al., Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation, FASEB J., 2005, vol. 19, no. 7, p. 786.
Carter, H.N. and Hood, D.A., Contractile activityinduced mitochondrial biogenesis and mTORC1, Am. J. Physiol. Cell Physiol., 2012, vol. 303, no. 5, p. 540.
Phillips, S.M., Parise, G., Roy, B.D., et al., Resistance-training-induced adaptations in skeletal muscle protein turnover in the fed state, Can. J. Physiol. Pharmacol., 2002, vol. 80, no. 11, p. 1045.
Apró, W., Wang, L., and Pontén, M., Resistance exercise induced mtorc1 signaling is not impaired by subsequent endurance exercise in human skeletal muscle, Am. J. Physiol. Endocrinol. Metab., 2013, vol. 305, no. 1, p. E22.
Apró, W., Moberg, M., Hamilton, D.L., et al., Resistance exercise-induced S6K1 kinase activity is not inhibited in human skeletal muscle despite prior activation of AMPK by high-intensity interval cycling, Am. J. Physiol. Endocrinol. Metab., 2015, vol. 308, no. 6, p. E470.
Wang, L., Mascher, H., Psilander, N., et al., Resistance exercise enhances the molecular signaling of mitochondrial biogenesis induced by endurance exercise in human skeletal muscle, J. Appl. Physiol., 2011, vol. 111, no. 5, p. 1335.
Psilander, N., Frank, P., Flockhart, M., and Sahlin, K., Adding strength to endurance training does not enhance aerobic capacity in cyclists, Scand. J. Med. Sci. Sports, 2014, vol. 25, no. 4, p. 353.
Nielsen, J.N., Mustard, K.J., Graham, D.A., et al., 5'- AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle, J. Appl. Physiol., 2003, vol. 94, no. 2, p. 631.
Perry, C.G., Lally, J., Holloway, G.P., et al., Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle, J. Physiol., 2010, vol. 588, p. 4795.
Schmutz, S., Dapp, C., Wittwer, M., et al., Endurance training modulates the muscular transcriptome response to acute exercise, Pflügers Arch., 2006, vol. 451, no. 5, p. 678.
Yu, M., Stepto, N.K., Chibalin, A.V., et al., Metabolic and mitogenic signal transduction in human skeletal muscle after intense cycling exercise, J. Physiol., 2003, vol. 546, p. 327.
Psilander, N., Frank, P., Flockhart, M., and Sahlin, K., Exercise with low glycogen increases PGC-1alpha gene expression in human skeletal muscle, Eur. J. Appl. Physiol., 2013, vol. 113, no. 4, p. 951.
Popov, D., Zinovkin, R., Karger, E., et al., Effects of continuous and intermittent aerobic exercise upon mRNA expression of metabolic genes in human skeletal muscle, J. Sports Med. Phys. Fitness, 2014, vol. 54, no. 3, p. 362.
Henselmans, M. and Schoenfeld, B.J., The effect of inter-set rest intervals on resistance exercise-induced muscle hypertrophy, Sports Med., 2014, vol. 44, no. 12, p. 1635.
Radaelli, R., Fleck, S.J., Leite, T., et al., Doseresponse of 1, 3, and 5 sets of resistance exercise on strength, local muscular endurance, and hypertrophy, J. Strength Cond. Res., 2015, vol. 29, no. 5, p. 1349.
Schoenfeld, B.J., Wilson, J.M., Lowery, R.P., and Krieger, J.W., Muscular adaptations in low–versus high-load resistance training: a meta-analysis, Eur. J. Sport Sci., 2014, vol. 16, no. 1, p. 1.
Hayot, M., Michaud, A., Koechlin, C., et al., Skeletal muscle microbiopsy: a validation study of a minimally invasive technique, Eur. Respir. J., 2005, vol. 25, no. 3, p. 431.
Sale, D.G., MacDougall, J.D., Jacobs, I., and Garner, S., Interaction between concurrent strength and endurance training, J. Appl. Physiol., 1990, vol. 68, no. 1, p. 260.
Paula-Gomes, S., Gonçalves, D.A., Baviera, A.M., et al., Insulin suppresses atrophy- and autophagyrelated genes in heart tissue and cardiomyocytes through AKT/FOXO signaling, Horm. Metab. Res., 2013, vol. 45, no. 12, p. 849.
Clarke, B.A., Drujan, D., Willis, M.S., et al., The E3 Ligase MuRF1 degrades myosin heavy chain protein in dexamethasone-treated skeletal muscle, Cell Metab., 2007, vol. 6, no. 5, p. 376.
Krawiec, B.J., Nystrom, G.J., Frost, R.A., et al., AMP-activated protein kinase agonists increase mRNA content of the muscle-specific ubiquitin ligases MAFbx and MuRF1 in C2C12 cells, Am. J. Physiol. Endocrinol. Metab., 2007, vol. 292, no. 6, p. E1555.
Nakashima, K. and Yakabe, Y., AMPK activation stimulates myofibrillar protein degradation and expression of atrophy-related ubiquitin ligases by increasing FOXO transcription factors in C2C12 myotubes, Biosci. Biotechnol. Biochem., 2007, vol. 71, no. 7, p. 1650.
Coffey, V.G., Zhong, Z., Shield, A., et al., Early signaling responses to divergent exercise stimuli in skeletal muscle from well-trained humans, FASEB J., 2006, vol. 20, no. 1, p. 190.
Greenhaff, P.L., Karagounis, L.G., Peirce, N., et al., Disassociation between the effects of amino acids and insulin on signaling, ubiquitin ligases, and protein turnover in human muscle, Am. J. Physiol. Endocrinol. Metab., 2008, vol. 295, no. 3, p. E595.
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Original Russian Text © E.A. Lysenko, D.V. Popov, T.F. Vepkhvadze, E.M. Lednev, O.L. Vinogradova, 2016, published in Fiziologiya Cheloveka, 2016, Vol. 42, No. 6, pp. 58–69.
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Lysenko, E.A., Popov, D.V., Vepkhvadze, T.F. et al. Effect of combined aerobic and strength exercises on the regulation of mitochondrial biogenesis and protein synthesis and degradation in human skeletal muscle. Hum Physiol 42, 634–644 (2016). https://doi.org/10.1134/S0362119716060104
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DOI: https://doi.org/10.1134/S0362119716060104