PGC‐1 isoforms and their target genes are expressed differently in human skeletal muscle following resistance and endurance exercise
The primary aim of the present study was to investigate the acute gene expression responses of PGC‐1 isoforms and PGC‐1α target genes related to mitochondrial biogenesis (cytochrome C), angiogenesis (VEGF‐A), and muscle hypertrophy (myostatin), after a resistance or endurance exercise bout. In addition, the study aimed to elucidate whether the expression changes of studied transcripts were linked to phosphorylation of AMPK and MAPK p38. Nineteen physically active men were divided into resistance exercise (RE, n = 11) and endurance exercise (EE, n = 8) groups. RE group performed leg press exercise (10 × 10 RM, 50 min) and EE walked on a treadmill (~80% HRmax, 50 min). Muscle biopsies were obtained from the vastus lateralis muscle before, 30 min, and 180 min after exercise. EE and RE significantly increased the gene expression of alternative promoter originated PGC‐1α exon 1b‐ and 1bxs'‐derived isoforms, whereas the proximal promoter originated exon 1a‐derived transcripts were less inducible and were upregulated only after EE. Truncated PGC‐1α transcripts were upregulated both after EE and RE. Neither RE nor EE affected the expression of PGC‐1β. EE upregulated the expression of cytochrome C and VEGF‐A, whereas RE upregulated VEGF‐A and downregulated myostatin. Both EE and RE increased the levels of p‐AMPK and p‐MAPK p38, but these changes were not linked to the gene expression responses ofPGC‐1 isoforms. The present study comprehensively assayed PGC‐1 transcripts in human skeletal muscle and showed exercise mode‐specific responses thus improving the understanding of early signaling events in exercise‐induced muscle adaptations.
Keywords:
PGC1-1b, PGC-1a, physical activity, splice variant.
Autoři:
Mika Silvennoinen *,1; Juha P. Ahtiainen 1; Juha J. Hulmi 1; Satu Pekkala 2; Ritva S. Taipale 1; Bradley C. Nindl 3; Tanja Laine 1; Keijo Häkkinen 1; Harri Selänne 4,5; Heikki Kyröläinen 1; Heikki Kainulainen 1
Působiště autorů:
Department of Biology of Physical Activity, University of Jyväskylä, Jyväskylä, Finland
1; Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
2; The Military Performance Division, The Unites States Army Research Institute of Environmental Medicine, Natick, Massachusetts
3; Jyväskylä Central Hospital, Jyväskylä, Finland
4; LIKES Research Center for Sport and Health Sciences, Jyväskylä, Finland
5
Vyšlo v časopise:
Physiological Reports, 3, 2015, č. 10, s. 1-12
Kategorie:
Original Research
prolekare.web.journal.doi_sk:
https://doi.org/10.14814/phy2.12563
© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Souhrn
The primary aim of the present study was to investigate the acute gene expression responses of PGC‐1 isoforms and PGC‐1α target genes related to mitochondrial biogenesis (cytochrome C), angiogenesis (VEGF‐A), and muscle hypertrophy (myostatin), after a resistance or endurance exercise bout. In addition, the study aimed to elucidate whether the expression changes of studied transcripts were linked to phosphorylation of AMPK and MAPK p38. Nineteen physically active men were divided into resistance exercise (RE, n = 11) and endurance exercise (EE, n = 8) groups. RE group performed leg press exercise (10 × 10 RM, 50 min) and EE walked on a treadmill (~80% HRmax, 50 min). Muscle biopsies were obtained from the vastus lateralis muscle before, 30 min, and 180 min after exercise. EE and RE significantly increased the gene expression of alternative promoter originated PGC‐1α exon 1b‐ and 1bxs'‐derived isoforms, whereas the proximal promoter originated exon 1a‐derived transcripts were less inducible and were upregulated only after EE. Truncated PGC‐1α transcripts were upregulated both after EE and RE. Neither RE nor EE affected the expression of PGC‐1β. EE upregulated the expression of cytochrome C and VEGF‐A, whereas RE upregulated VEGF‐A and downregulated myostatin. Both EE and RE increased the levels of p‐AMPK and p‐MAPK p38, but these changes were not linked to the gene expression responses ofPGC‐1 isoforms. The present study comprehensively assayed PGC‐1 transcripts in human skeletal muscle and showed exercise mode‐specific responses thus improving the understanding of early signaling events in exercise‐induced muscle adaptations.
Keywords:
PGC1-1b, PGC-1a, physical activity, splice variant.
Zdroje
1. Ahtiainen, J. P., S. Walker, M. Silvennoinen, H. Kyröläinen, B. C. Nindl, K. Häkkinen, et al. 2015. Exercise type and volume alter signaling pathways regulating skeletal muscle glucose uptake and protein synthesis. Eur. J. Appl. Physiol. 115:1835–1845.
2. Atherton, P. J., J. Babraj, K. Smith, J. Singh, M. J. Rennie, and H. Wackerhage. 2005. 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. 19:786–788.
3. Baar, K., and K. Esser. 1999. Phosphorylation of p70(S6k) correlates with increased skeletal muscle mass following resistance exercise. Am. J. Physiol. 276:C120–C127.
4. Baar, K., A. R. Wende, T. E. Jones, M. Marison, L. A. Nolte, M. Chen, et al. 2002. Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1. FASEB J. 16:1879–1886.
5. Bartlett, J.D., C. Hwa Joo, T. S. Jeong, J. Louhelainen, A. J. Cochran, M. J. Gibala, et al. 2012. Matched work high- intensity interval and continuous running induce similar increases in PGC-1alpha mRNA, AMPK, p38, and p53 phosphorylation in human skeletal muscle. J. Appl. Physiol. (1985) 112:1135–1143.
6. Canto, C., L. Q. Jiang, A. S. Deshmukh, C. Mataki, A. Coste, M. Lagouge, et al. 2010. Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab. 11:213–219.
7. Chinsomboon, J., J. Ruas, R. K. Gupta, R. Thom, J. Shoag, G. C. Rowe, et al. 2009. The transcriptional coactivator PGC-1alpha mediates exercise-induced angiogenesis in skeletal muscle. Proc. Natl. Acad. Sci. U. S. A. 106:21401– 21406.
8. Egan, B., B. P. Carson, P. M. Garcia-Roves, A. V. Chibalin, F. M. Sarsfield, N. Barron, et al. 2010. Exercise intensity- dependent regulation of peroxisome proliferator-activated receptor coactivator-1 mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle. J. Physiol. 588:1779–1790.
9. Gibala, M. 2009. Molecular responses to high-intensity interval exercise. Appl. Physiol. Nutr. Metab. 34:428–432.
10. Gidlund, E. K., M. Ydfors, S. Appel, H. Rundqvist, C. J. Sundberg, and J. M. Norrbom. 2015. Rapidly elevated levels of PGC-1alpha-b protein in human skeletal muscle after exercise: exploring regulatory factors in a randomized controlled trial. J. Appl. Physiol. (1985) 119:374–384.
11. Hawley, J. A., M. Hargreaves, M. J. Joyner, and J. R. Zierath. 2014. Integrative biology of exercise. Cell 159:738–749.
12. Holloszy, J. O., and F. W. Booth. 1976. Biochemical adaptations to endurance exercise in muscle. Annu. Rev. Physiol. 38:273–291.
13. Hulmi, J. J., J. P. Ahtiainen, T. Kaasalainen, E. Pöllänen, K. Häkkinen, M. Alen, et al. 2007. Post exercise myostatin and activin IIb mRNA levels: effects of strength training. Med. Sci. Sports Exerc. 39:289–297.
14. Hulmi, J. J., S. Walker, J. P. Ahtiainen, K. Nyman, W. J. Kraemer, and K. Häkkinen. 2012. Molecular signaling in muscle is affected by the specificity of resistance exercise protocol. Scand. J. Med. Sci. Sports 22:240–248.
15. Kim, J. S., J. K. Petrella, J. M. Cross, and M. M. Bamman. 2007. Load-mediated downregulation of myostatin mRNA is not sufficient to promote myofiber hypertrophy in humans: a cluster analysis. J. Appl. Physiol. (1985) 103:1488–1495.
16. Koressaar, T., and M. Remm. 2007. Enhancements and modifications of primer design program Primer3. Bioinformatics 23:1289–1291.
17. Lundberg, T. R., R. Fernandez-Gonzalo, J. Norrbom, H. Fischer, P. A. Tesch, and T. Gustafsson. 2014. Truncated splice variant PGC-1alpha4 is not associated with exercise- induced human muscle hypertrophy. Acta Physiol. (Oxf) 212:142–151.
18. Lundby, C., N. Nordsborg, K. Kusuhara, K. M. Kristensen, P. D. Neufer, and H. Pilegaard. 2005. Gene expression in human skeletal muscle: alternative normalization method and effect of repeated biopsies. Eur. J. Appl. Physiol. 95:351–360.
19. Meirhaeghe, A., V. Crowley, C. Lenaghan, C. Lelliott, K. Green, A. Stewart, et al. 2003. Characterization of the human, mouse and rat PGC1 beta (peroxisome-proliferator- activated receptor-gamma co-activator 1 beta) gene in vitro and in vivo. Biochem. J. 373:155–165.
20. Miura, S., Y. Kai, Y. Kamei, and O. Ezaki. 2008. Isoform-specific increases in murine skeletal muscle peroxisome proliferator- activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to beta2-adrenergic receptor activation and exercise. Endocrinology 149:4527–4533.
21. Norrbom, J., E. K. Sallstedt, H. Fischer, C. J. Sundberg, H. Rundqvist, and T. Gustafsson. 2011. Alternative splice variant PGC-1alpha-b is strongly induced by exercise in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 301:E1092–E1098.
22. Olesen, J., K. Kiilerich, and H. Pilegaard. 2010. PGC-1alpha- mediated adaptations in skeletal muscle. Pflugers Arch. 460:153–162.
23. Pilegaard, H., B. Saltin, and P. D. Neufer. 2003. Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. J. Physiol. 546:851–858.
24. Popov, D. V., A. V. Bachinin, E. A. Lysenko, T. F. Miller, and O. L. Vinogradova. 2014. Exercise-induced expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha isoforms in skeletal muscle of endurance- trained males. J. Physiol. Sci. 64:317–323.
25. Ranhotra, H. S. 2010. Long-term caloric restriction up- regulates PPAR gamma co-activator 1 alpha (PGC-1alpha) expression in mice. Indian J. Biochem. Biophys. 47:272–277.
26. Ruas, J. L., J. P. White, R. R. Rao, S. Kleiner, K. T. Brannan, B. C. Harrison, et al. , et al. 2012. A PGC-1alpha isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell 151:1319–1331.
27. Sriwijitkamol, A., D. K. Coletta, E. Wajcberg, G. B. Balbontin, S. M. Reyna, J. Barrientes, et al. 2007. Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes: a time-course and dose-response study. Diabetes 56:836–848.
28. Thom, R., G. C. Rowe, C. Jang, A. Safdar, and Z. Arany. 2014. Hypoxic induction of vascular endothelial growth factor (VEGF) and angiogenesis in muscle by truncated peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha. J. Biol. Chem. 289:8810–8817.
29. Untergasser, A., I. Cutcutache, T. Koressaar, J. Ye, B. C. Faircloth, M. Remm, et al. 2012. Primer3–new capabilities and interfaces. Nucleic Acids Res. 40:e115.
30. Wen, X., J. Wu, J. S. Chang, P. Zhang, J. Wang, Y. Zhang, et al. 2014. Effect of exercise intensity on isoform-specific expressions of NT-PGC-1 alpha mRNA in mouse skeletal muscle. Biomed. Res. Int. 2014:402175.
31. Ydfors, M., H. Fischer, H. Mascher, E. Blomstrand, J. Norrbom, and T. Gustafsson. 2013. The truncated splice variants, NT-PGC-1alpha and PGC-1alpha4, increase with both endurance and resistance exercise in human skeletal muscle. Physiol. Rep. 1:e00140.
32. Zhang, Y., P. Huypens, A. W. Adamson, J. S. Chang, T. M. Henagan, A. Boudreau, et al. 2009. Alternative mRNA splicing produces a novel biologically active short isoform of PGC-1alpha. J. Biol. Chem. 284:32813–32826.
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