Progressive Resistance Training Modulates the Expression of ACTN2 and ACTN3 Genes and Proteins in the Skeletal Muscles

Neda khaledi^1, , Rana Fayazmilani², Abbas Ali Gaeini³ and Arash Javeri⁴

¹Exercise Physiology, Kharazmi University

²Exercise Physiology, Shahid Beheshti University

³Exercise Physiology, The University of Tehran

⁴Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

Cite this paper

Neda khaledi, Rana Fayazmilani, Abbas Ali Gaeini and Arash Javeri. Progressive Resistance Training Modulates the Expression of ACTN2 and ACTN3 Genes and Proteins in the Skeletal Muscles. American Journal of Sports Science and Medicine. 2016; 4(2):26-32. doi: 10.12691/AJSSM-4-2-1

Abstract

Purpose: Mammalian skeletal muscle has the two isoforms of actin binding protein, α-Actinin-2 and α-Actinin-3, which are located in the skeletal muscle Z-line where they cross-link the actin thin filaments. There is a common stop codon polymorphism R577X in the ACTN3 gene. Several association studies have demonstrated that the ACTN3 R577X genotype influences athletic performance. The response of α-Actinins to resistance exercise training is little understood. Methods: Female Sprague-Dawley rats were assigned to control (C; n = 10) and resistance training (T; n = 12) groups. Training consisted of climbing a ladder carrying a load suspended from the tail. After training, fast (Flexor halluces longus, FHL) and slow (Soleus) hind limb muscles from each group was examine to study the effect of resistance training on muscle mass. Gene expression and protein levels of both Actn3, Actn2 were examined. Results: The resistance trained group had a significantly greater absolute muscle mass in FHL (P=0.011). We also found that Actn3 and Actn2 gene expression levels increased significantly in FHL and Soleus muscles by mean factors of 2.16, and 2.91, respectively. α-Actinin-2 protein expression increased significantly in training group (P=0.025) while, α-actinin-3 protein expression remained similar in training & control groups (P=0.130). The most important finding of this study showed that both α-actinin-3 and α-actinin-2 mRNA levels were up-regulated after 8wk of resistance training (P≤0.05). Conclusion: Our results provide a new insight into the impact of progressive resistance training and evaluating the role of α-actinins responsiveness.

Keywords

vertical ladder, α–actinins, sarcomere, Z-line, resistance training

Copyright

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References

[1]	AHMETOV, II, DRUZHEVSKAYA, A. M., ASTRATENKOVA, I. V., POPOV, D. V., VINOGRADOVA, O. L. & ROGOZKIN, V. A. 2010. The ACTN3 R577X polymorphism in Russian endurance athletes. Br J Sports Med, 44, 649-52.
[2]	AUSTRALIA. ANTARCTIC ANIMAL CARE AND IONISING RADIATION USAGE COMMITTEE., AUSTRALIA. DEPT. OF THE ARTS SPORT THE ENVIRONMENT AND TERRITORIES., AUSTRALIA. ANTARCTIC DIVISION. & AUSTRALIAN NATIONAL ANTARCTIC RESEARCH EXPEDITIONS. Guidelines for research involving animal experimentation or use of ionising radiation. Hobart, Tasmania: Commonwealth of Australia.
[3]	BOOTH, F. W., TSENG, B. S., FLUCK, M. & CARSON, J. A. 1998. Molecular and cellular adaptation of muscle in response to physical training. Acta Physiol Scand, 162, 343-50.
[4]	CARTER, E. E., THOMAS, M. M., MURYNKA, T., ROWAN, S. L., WRIGHT, K. J., HUBA, E. & HEPPLE, R. T. 2010. Slow twitch soleus muscle is not protected from sarcopenia in senescent rats. Exp Gerontol, 45, 662-70.
[5]	CLARKSON, P. M., DEVANEY, J. M., GORDISH-DRESSMAN, H., THOMPSON, P. D., HUBAL, M. J., URSO, M., PRICE, T. B., ANGELOPOULOS, T. J., GORDON, P. M., MOYNA, N. M., PESCATELLO, L. S., VISICH, P. S., ZOELLER, R. F., SEIP, R. L. & HOFFMAN, E. P. 2005. ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women. J Appl Physiol, 99, 154-63.
[6]	DELMONICO, M. J., KOSTEK, M. C., DOLDO, N. A., HAND, B. D., WALSH, S., CONWAY, J. M., CARIGNAN, C. R., ROTH, S. M. & HURLEY, B. F. 2007. Alpha-actinin-3 (ACTN3) R577X polymorphism influences knee extensor peak power response to strength training in older men and women. J Gerontol A Biol Sci Med Sci, 62, 206-12.
[7]	DELMONICO, M. J., ZMUDA, J. M., TAYLOR, B. C., CAULEY, J. A., HARRIS, T. B., MANINI, T. M., SCHWARTZ, A., LI, R., ROTH, S. M., HURLEY, B. F., BAUER, D. C., FERRELL, R. E. & NEWMAN, A. B. 2008. Association of the ACTN3 genotype and physical functioning with age in older adults. J Gerontol A Biol Sci Med Sci, 63, 1227-34.
[8]	EYNON, N., DUARTE, J. A., OLIVEIRA, J., SAGIV, M., YAMIN, C., MECKEL, Y. & GOLDHAMMER, E. 2009. ACTN3 R577X polymorphism and Israeli top-level athletes. Int J Sports Med, 30, 695-8.
[9]	FARRELL, P. A., FEDELE, M. J., HERNANDEZ, J., FLUCKEY, J. D., MILLER, J. L., 3RD, LANG, C. H., VARY, T. C., KIMBALL, S. R. & JEFFERSON, L. S. 1999. Hypertrophy of skeletal muscle in diabetic rats in response to chronic resistance exercise. J Appl Physiol, 87, 1075-82.
[10]	FRANK, D., KUHN, C., KATUS, H. A. & FREY, N. 2006. The sarcomeric Z-disc: a nodal point in signalling and disease. J Mol Med, 84, 446-68.
[11]	GARTON, F. C., SETO, J. T., QUINLAN, K. G., YANG, N., HOUWELING, P. J. & NORTH, K. N. 2014. alpha-Actinin-3 deficiency alters muscle adaptation in response to denervation and immobilization. Hum Mol Genet, 23, 1879-93.
[12]	GLASS, D. J. 2003. Molecular mechanisms modulating muscle mass. Trends Mol Med, 9, 344-50.
[13]	HADDAD, F., QIN, A. X., ZENG, M., MCCUE, S. A. & BALDWIN, K. M. 1998. Effects of isometric training on skeletal myosin heavy chain expression. J Appl Physiol, 84, 2036-41.
[14]	HORNBERGER TA JR, F. R. 2004. Physiological hypertrophy of the FHL muscle following 8 weeks of progressive resistance exercise in the rat. Can J Appl Physiol, 29, 16-31.
[15]	MACARTHUR, D. G. & NORTH, K. N. 2004. A gene for speed? The evolution and function of alpha-actinin-3. Bioessays, 26, 7. 96-86.
[16]	MACARTHUR, D. G. & NORTH, K. N. 2007. ACTN3: A genetic influence on muscle function and athletic performance. Exerc Sport Sci Rev, 35, 30-4.
[17]	MACARTHUR, D. G., SETO, J. T., CHAN, S., QUINLAN, K. G., RAFTERY, J. M., TURNER, N., NICHOLSON, M. D., KEE, A. J., HARDEMAN, E. C., GUNNING, P. W., COONEY, G. J., HEAD, S. I., YANG, N. & NORTH, K. N. 2008. An Actn3 knockout mouse provides mechanistic insights into the association between alpha-actinin-3 deficiency and human athletic performance. Hum Mol Genet, 86-1076; 7.
[18]	MASSIDDA, M., VONA, G. & CALO, C. M. 2009. Association between the ACTN3 R577X polymorphism and artistic gymnastic performance in Italy. Genet Test Mol Biomarkers, 13, 377-80.
[19]	MILLS, M., YANG, N., WEINBERGER, R., VANDER WOUDE, D. L., BEGGS, A. H., EASTEAL, S. & NORTH, K. 2001. Differential expression of the actin-binding proteins, alpha-actinin-2 and -3, in different species: implications for the evolution of functional redundancy. Hum Mol Genet, 10, 1335-46.
[20]	NORMAN, B., ESBJORNSSON, M., RUNDQVIST, H., OSTERLUND, T., VON WALDEN, F. & TESCH, P. A. 2009. Strength, power, fiber types, and mRNA expression in trained men and women with different ACTN3 R577X genotypes. J Appl Physiol, 106, 959-65.
[21]	NORTH, K. 2008. Why is alpha-actinin-3 deficiency so common in the general population? The evolution of athletic performance. Twin Res Hum Genet, 11, 384-94.
[22]	OGURA, Y., NAITO, H., KAKIGI, R., AKEMA, T., SUGIURA, T., KATAMOTO, S. & AOKI, J. 2009. Different adaptations of alpha-actinin isoforms to exercise training in rat skeletal muscles. Acta Physiol (Oxf), 196, 341-9.
[23]	PAPADIMITRIOU, I. D., PAPADOPOULOS, C., KOUVATSI, A. & TRIANTAPHYLLIDIS, C. 2008. The ACTN3 gene in elite Greek track and field athletes. Int J Sports Med, 29, 352-5.
[24]	RUIZ, J. R., FERNANDEZ DEL VALLE, M., VERDE, Z., DIEZ-VEGA, I., SANTIAGO, C., YVERT, T., RODRIGUEZ-ROMO, G., GOMEZ-GALLEGO, F., MOLINA, J. J. & LUCIA, A. 2010. ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players. Scand J Med Sci Sports.
[25]	SCOTT, R. A., IRVING, R., IRWIN, L., MORRISON, E., CHARLTON, V., AUSTIN, K., TLADI, D., DEASON, M., HEADLEY, S. A., KOLKHORST, F. W., YANG, N., NORTH, K. & PITSILADIS, Y. P. 2010. ACTN3 and ACE genotypes in elite Jamaican and US sprinters. Med Sci Sports Exerc, 42, 107-12.
[26]	SETO, J. T., CHAN, S., TURNER, N., MACARTHUR, D. G., RAFTERY, J. M., BERMAN, Y. D., QUINLAN, K. G., COONEY, G. J., HEAD, S., YANG, N. & NORTH, K. N. 2011. The effect of alpha-actinin-3 deficiency on muscle aging. Exp Gerontol, 4. 302-692, 6.
[27]	SETO, J. T., QUINLAN, K. G., LEK, M., ZHENG, X. F., GARTON, F., MACARTHUR, D. G., HOGARTH, M. W., HOUWELING, P. J., GREGOREVIC, P., TURNER, N., COONEY, G. J., YANG, N. & NORTH, K. N. 2013. ACTN3 genotype influences muscle performance through the regulation of calcineurin signaling. J Clin Invest, 123, 4255-63.
[28]	TOIGO, M. & BOUTELLIER, U. 2006. New fundamental resistance exercise determinants of molecular and cellular muscle adaptations. Eur J Appl Physiol, 97, 643-63.
[29]	VINCENT, B., DE BOCK, K., RAMAEKERS, M., VAN DEN EEDE, E., VAN LEEMPUTTE, M., HESPEL, P. & THOMIS, M. A. 2007. ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics, 32, 58-63.
[30]	YANG, N., MACARTHUR, D. G., GULBIN, J. P., HAHN, A. G., BEGGS, A. H., EASTEAL, S. & NORTH, K. 2003. ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet, 73, 627-31.
[31]	YU, J. G., FURST, D. O. & THORNELL, L. E. 2003. The mode of myofibril remodelling in human skeletal muscle affected by DOMS induced by eccentric contractions. Histochem Cell Biol, 119, 383-93.