اثر تمرین اینتروال شدید بر بیان ژن‌های TRAF6 و MuRF1 در عضلۀ بازکنندۀ طویل انگشتان پای موش‌های پیر

نوع مقاله: مقاله پژوهشی

نویسندگان

1 دانشیار فیزیولوژی ورزشی، گروه علوم ورزشی، دانشکدۀ ادبیات و علوم انسانی، دانشگاه ولی‌عصر (عج)، رفسنجان، ایران

2 کارشناسی ارشد فیزیولوژی ورزشی، گروه فیزیولوژی ورزشی، دانشکدۀ ادبیات و علوم انسانی، دانشگاه آزاد اسلامی، کرمان، ایران

چکیده

یکی از سازوکارهای دخیل در آتروفی عضلانی مسیر TRAF6/MuRF1 است که ممکن است تجزیۀ عضلانی را افزایش دهد. ازاین‌رو هدف پژوهش حاضر بررسی اثر تمرین HIIT بر بیان ژن‌های TRAF6 و MuRF1 عضلۀ بازکنندۀ طویل انگشتان پای ((EDL موش‌های پیر C57bl/6 بود. بدین‌منظور، 28 سر موش C57bl/6 پیر (14=n) و بالغ (14=n) هر گروه در 2 گروه تمرین (7=n) و کنترل (7=n) قرار گرفتند که گروه‌های تمرین بعد از یک هفته آشناسازی در برنامۀ 4 هفته HIIT شرکت کردند و 48 ساعت پس از آخرین جلسۀ تمرینی قربانی و عضلۀ EDL استخراج و به‌وسیلۀ روش Real-time Pcr بیان ژن‌ها اندازه‌گیری شد. در مقایسۀ گروه‌های پیر و بالغ، عامل پیری اثر معنا‌داری بر بیان ژن‌های TRAF6 و MuRF1 دارد (به‌ترتیب 005/0=P و 004/0=P)، همچنین تمرین ورزشی به‌طور چشمگیری بیان این دو را تحت تأثیر قرار می‌دهد (0001/0=P). همچنین یافته‌ها نشان می‌دهد که پیری اثر معنا‌داری بر وزن نسبی عضله EDL داشته است، به‌طوری‌که اختلاف معنا‌داری بین گروه‌های بالغ و پیر کنترل (032/0=P) مشاهده شد، ولی این مقدار به لحاظ آماری در هر دو گروه‌های بالغ (117/0=P) و پیر (321/0=P) معنادار نبود. بنابراین، بالا رفتن سن همراه با افزایش بیان ژن‌های TRAF6 و MuRF1 است که احتمالاً در تغییرات تودۀ عضلانی همراه با افزایش سن درگیرند و با توجه به اینکه تمرینات با شدت بالا بیان این ژن‌ها را کاهش می‌دهد، این تمرینات می‌توانند در دوران سالمندی به‌منظور حفظ تودۀ عضلانی استفاده شوند.

کلیدواژه‌ها


عنوان مقاله [English]

The Effect of High Intensity Interval Training on Gene Expression of MuRF1 and TRAF6 in Extensor Digitorum Longus (EDL) Muscle of Aged Mice

نویسندگان [English]

  • abdolreza kazemi 1
  • salaman barbat 2
1 Associate Professor in Exercise Physiology, Department of Sport Sciences, Faculty of Literature and Humanities, Va-i E-Asr University, Rafsanjan, Iran
2 MSc in Exercise Physiology, Department of Exercise Physiology, Faculty of Literature and Humanities, Islamic Azad University, Kerman , Iran
چکیده [English]

One of the mechanisms involved in muscle atrophy is TRAF6/MuRF1 path, which may increase muscle breakdown. The aim of the present study was to investigate the effect of high intensity interval training (HIIT) on gene expression of MuRF1 andTRAF6in EDL muscle of aged C57bl/6 mice.  For this purpose, 28 C57bl/6 aged (n=14) and adult (n=14) mice of each group were assigned to two groups: training (n=7) and control (n=7). After one week of familiarization, training groups participated in 4 weeks of HIIT program. The mice were sacrificed 48 hours after the last training session and their EDL muscle were extracted and the gene expressions were measured with Real-time PCR technique. The comparison of aged and adult groups showed that aging had a significant effect on MuRF1 and TRAF6 mRNA gene expression (P=0.005 and P=0.004 respectively). Also, training drastically influenced MuRF1 and TRAF6 expression (P=0.0001). The findings also showed that aging had a significant effect on EDL muscle weight as a significant difference was observed between aging and adult control groups (P=0.032). But this amount was not statistically significant in both adult (P=0.117) and aged (P=0.321) groups. Thus, aging is associated with an increase in MuRF1 andTRAF6gene expression, which could possibly be involved in muscle mass changes associated with aging. Since high intensity interval training decrease the expression of these genes, it can be utilized to maintain muscle mass during aging.

کلیدواژه‌ها [English]

  • Aging
  • high intensity interval training
  • MuRF1
  • muscle mass
  • TRAF6
1.   Fanzani A, Conraads VM, Penna F, Martinet W. Molecular and cellular mechanisms of skeletal muscle atrophy: an update. Journal of cachexia, sarcopenia and muscle. 2012;3(3):163-79.

2.   Paul PK, Gupta SK, Bhatnagar S, Panguluri SK, Darnay BG, Choi Y, et al. Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice. The Journal of cell biology. 2010;191(7):1395-411.

3.   Lexell J, Taylor CC, Sjöström M. What is the cause of the ageing atrophy?: Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15-to 83-year-old men. Journal of the neurological sciences. 1988;84(2-3):275-94.

4.   Verdijk LB, Koopman R, Schaart G, Meijer K, Savelberg HH, van Loon LJ. Satellite cell content is specifically reduced in type II skeletal muscle fibers in the elderly. American Journal of Physiology-Endocrinology and Metabolism. 2007;292(1):E151-E7.

5.   Rowan SL, Rygiel K, Purves-Smith FM, Solbak NM, Turnbull DM, Hepple RT. Denervation causes fiber atrophy and myosin heavy chain co-expression in senescent skeletal muscle. PloS one. 2012;7(1):e29082.

6.   Bialek P, Morris C, Parkington J, St. Andre M, Owens J, Yaworsky P, et al. Distinct protein degradation profiles are induced by different disuse models of skeletal muscle atrophy. Physiological genomics. 2011;43(19):1075-86.

7.   Paul PK, Bhatnagar S, Mishra V, Srivastava S, Darnay BG, Choi Y, et al. The E3 ubiquitin ligase TRAF6 intercedes in starvation-induced skeletal muscle atrophy through multiple mechanisms. Molecular and cellular biology. 2012;32(7):1248-59.

8.   Sun H, Gong Y, Qiu J, Chen Y, Ding F, Zhao Q. TRAF6 inhibition rescues dexamethasone-induced muscle atrophy. International journal of molecular sciences. 2014;15(6):11126-41.

9.   Aagaard P, Suetta C, Caserotti P, Magnusson SP, Kjær M. Role of the nervous system in sarcopenia and muscle atrophy with aging: strength training as a countermeasure. Scandinavian journal of medicine & science in sports. 2010;20(1):49-64.

10. Sheffield-Moore M, Yeckel C, Volpi E, Wolf S, Morio B, Chinkes D, et al. Postexercise protein metabolism in older and younger men following moderate-intensity aerobic exercise. American Journal of Physiology-Endocrinology and Metabolism. 2004;287(3):E513-E22.

11. Raue U, Slivka D, Jemiolo B, Hollon C, Trappe S. Myogenic gene expression at rest and after a bout of resistance exercise in young (18–30 yr) and old (80–89 yr) women. Journal of Applied Physiology. 2006;101(1):53-9.

12. Gielen S, Sandri M, Kozarez I, Kratzsch J, Teupser D, Thiery J, et al. Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig Exercise Intervention in Chronic Heart Failure and Aging catabolism study. Circulation. 2012;125(22):2716-27.

13. Drey M, Krieger B, Sieber CC, Bauer JM, Hettwer S, Bertsch T, et al. Motoneuron loss is associated with sarcopenia. Journal of the American Medical Directors Association. 2014;15(6):435-9.

14. Glass DJ. Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nature cell biology. 2003;5(2):87.

15. Thomas C, Bishop D, Moore-Morris T, Mercier J. Effects of high-intensity training on MCT1, MCT4, and NBC expressions in rat skeletal muscles: influence of chronic metabolic alkalosis. American Journal of Physiology-Endocrinology and Metabolism. 2007;293(4):E916-E22.

16. Nilwik R, Snijders T, Leenders M, Groen BB, van Kranenburg J, Verdijk LB, et al. The decline in skeletal muscle mass with aging is mainly attributed to a reduction in type II muscle fiber size. Experimental gerontology. 2013;48(5):492-8.

17. Muller FL, Song W, Jang YC, Liu Y, Sabia M, Richardson A, et al. Denervation-induced skeletal muscle atrophy is associated with increased mitochondrial ROS production. American journal of physiology-Regulatory, integrative and comparative physiology. 2007;293(3):R1159-R68.

18. Bonaldo P, Sandri M. Cellular and molecular mechanisms of muscle atrophy. Disease models & mechanisms. 2013;6(1):25-39.

19. Sandri M, Barberi L, Bijlsma A, Blaauw B, Dyar K, Milan G, et al. Signalling pathways regulating muscle mass in ageing skeletal muscle. The role of the IGF1-Akt-mTOR-FoxO pathway. Biogerontology. 2013;14(3):303-23.

20. Morissette MR, Stricker JC, Rosenberg MA, Buranasombati C, Levitan EB, Mittleman MA, et al. Effects of myostatin deletion in aging mice. Aging cell. 2009;8(5):573-83.

21. Gomes AV, Waddell DS, Siu R, Stein M, Dewey S, Furlow JD, et al. Upregulation of proteasome activity in muscle RING finger 1-null mice following denervation. The FASEB Journal. 2012;26(7):2986-99.

22. GhadiriHormati L, Aminaei M, Dakhili AB. The Effect of High-Intensity Exercise Training on Gene Expression of Semaphorin 3A in Extensor Digitorum Longus Muscles ofAged C57bl/6 Mice. scientific journal of ilam university of medical sciences. 2017;25(1):92-102.

23. Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nature reviews immunology. 2011;11(9):607.

24. Argilés JM, Busquets S, Toledo M, López-Soriano FJ. The role of cytokines in cancer cachexia. Current opinion in supportive and palliative care. 2009;3(4):263-8.

25. Zapata JM, Lefebvre S, Reed JC. Targeting TRAfs for therapeutic intervention. TNF Receptor Associated Factors (TRAFs): Springer; 2007. p. 188-201.

26. Adams V, Mangner N, Gasch A, Krohne C, Gielen S, Hirner S, et al. Induction of MuRF1 is essential for TNF-α-induced loss of muscle function in mice. Journal of molecular biology. 2008;384(1):48-59.

27. Li Y-P, Chen Y, John J, Moylan J, Jin B, Mann DL, et al. TNF-α acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. The FASEB Journal. 2005;19(3):362-70.

28. Cunha TF, Bacurau AV, Moreira JB, Paixão NA, Campos JC, Ferreira JC, et al. Exercise training prevents oxidative stress and ubiquitin-proteasome system overactivity and reverse skeletal muscle atrophy in heart failure. PloS one. 2012;7(8):e41701.

 

 

1.   Fanzani A, Conraads VM, Penna F, Martinet W. Molecular and cellular mechanisms of skeletal muscle atrophy: an update. Journal of cachexia, sarcopenia and muscle. 2012;3(3):163-79.

2.   Paul PK, Gupta SK, Bhatnagar S, Panguluri SK, Darnay BG, Choi Y, et al. Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice. The Journal of cell biology. 2010;191(7):1395-411.

3.   Lexell J, Taylor CC, Sjöström M. What is the cause of the ageing atrophy?: Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15-to 83-year-old men. Journal of the neurological sciences. 1988;84(2-3):275-94.

4.   Verdijk LB, Koopman R, Schaart G, Meijer K, Savelberg HH, van Loon LJ. Satellite cell content is specifically reduced in type II skeletal muscle fibers in the elderly. American Journal of Physiology-Endocrinology and Metabolism. 2007;292(1):E151-E7.

5.   Rowan SL, Rygiel K, Purves-Smith FM, Solbak NM, Turnbull DM, Hepple RT. Denervation causes fiber atrophy and myosin heavy chain co-expression in senescent skeletal muscle. PloS one. 2012;7(1):e29082.

6.   Bialek P, Morris C, Parkington J, St. Andre M, Owens J, Yaworsky P, et al. Distinct protein degradation profiles are induced by different disuse models of skeletal muscle atrophy. Physiological genomics. 2011;43(19):1075-86.

7.   Paul PK, Bhatnagar S, Mishra V, Srivastava S, Darnay BG, Choi Y, et al. The E3 ubiquitin ligase TRAF6 intercedes in starvation-induced skeletal muscle atrophy through multiple mechanisms. Molecular and cellular biology. 2012;32(7):1248-59.

8.   Sun H, Gong Y, Qiu J, Chen Y, Ding F, Zhao Q. TRAF6 inhibition rescues dexamethasone-induced muscle atrophy. International journal of molecular sciences. 2014;15(6):11126-41.

9.   Aagaard P, Suetta C, Caserotti P, Magnusson SP, Kjær M. Role of the nervous system in sarcopenia and muscle atrophy with aging: strength training as a countermeasure. Scandinavian journal of medicine & science in sports. 2010;20(1):49-64.

10. Sheffield-Moore M, Yeckel C, Volpi E, Wolf S, Morio B, Chinkes D, et al. Postexercise protein metabolism in older and younger men following moderate-intensity aerobic exercise. American Journal of Physiology-Endocrinology and Metabolism. 2004;287(3):E513-E22.

11. Raue U, Slivka D, Jemiolo B, Hollon C, Trappe S. Myogenic gene expression at rest and after a bout of resistance exercise in young (18–30 yr) and old (80–89 yr) women. Journal of Applied Physiology. 2006;101(1):53-9.

12. Gielen S, Sandri M, Kozarez I, Kratzsch J, Teupser D, Thiery J, et al. Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig Exercise Intervention in Chronic Heart Failure and Aging catabolism study. Circulation. 2012;125(22):2716-27.

13. Drey M, Krieger B, Sieber CC, Bauer JM, Hettwer S, Bertsch T, et al. Motoneuron loss is associated with sarcopenia. Journal of the American Medical Directors Association. 2014;15(6):435-9.

14. Glass DJ. Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nature cell biology. 2003;5(2):87.

15. Thomas C, Bishop D, Moore-Morris T, Mercier J. Effects of high-intensity training on MCT1, MCT4, and NBC expressions in rat skeletal muscles: influence of chronic metabolic alkalosis. American Journal of Physiology-Endocrinology and Metabolism. 2007;293(4):E916-E22.

16. Nilwik R, Snijders T, Leenders M, Groen BB, van Kranenburg J, Verdijk LB, et al. The decline in skeletal muscle mass with aging is mainly attributed to a reduction in type II muscle fiber size. Experimental gerontology. 2013;48(5):492-8.

17. Muller FL, Song W, Jang YC, Liu Y, Sabia M, Richardson A, et al. Denervation-induced skeletal muscle atrophy is associated with increased mitochondrial ROS production. American journal of physiology-Regulatory, integrative and comparative physiology. 2007;293(3):R1159-R68.

18. Bonaldo P, Sandri M. Cellular and molecular mechanisms of muscle atrophy. Disease models & mechanisms. 2013;6(1):25-39.

19. Sandri M, Barberi L, Bijlsma A, Blaauw B, Dyar K, Milan G, et al. Signalling pathways regulating muscle mass in ageing skeletal muscle. The role of the IGF1-Akt-mTOR-FoxO pathway. Biogerontology. 2013;14(3):303-23.

20. Morissette MR, Stricker JC, Rosenberg MA, Buranasombati C, Levitan EB, Mittleman MA, et al. Effects of myostatin deletion in aging mice. Aging cell. 2009;8(5):573-83.

21. Gomes AV, Waddell DS, Siu R, Stein M, Dewey S, Furlow JD, et al. Upregulation of proteasome activity in muscle RING finger 1-null mice following denervation. The FASEB Journal. 2012;26(7):2986-99.

22. GhadiriHormati L, Aminaei M, Dakhili AB. The Effect of High-Intensity Exercise Training on Gene Expression of Semaphorin 3A in Extensor Digitorum Longus Muscles ofAged C57bl/6 Mice. scientific journal of ilam university of medical sciences. 2017;25(1):92-102.

23. Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nature reviews immunology. 2011;11(9):607.

24. Argilés JM, Busquets S, Toledo M, López-Soriano FJ. The role of cytokines in cancer cachexia. Current opinion in supportive and palliative care. 2009;3(4):263-8.

25. Zapata JM, Lefebvre S, Reed JC. Targeting TRAfs for therapeutic intervention. TNF Receptor Associated Factors (TRAFs): Springer; 2007. p. 188-201.

26. Adams V, Mangner N, Gasch A, Krohne C, Gielen S, Hirner S, et al. Induction of MuRF1 is essential for TNF-α-induced loss of muscle function in mice. Journal of molecular biology. 2008;384(1):48-59.

27. Li Y-P, Chen Y, John J, Moylan J, Jin B, Mann DL, et al. TNF-α acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. The FASEB Journal. 2005;19(3):362-70.

28. Cunha TF, Bacurau AV, Moreira JB, Paixão NA, Campos JC, Ferreira JC, et al. Exercise training prevents oxidative stress and ubiquitin-proteasome system overactivity and reverse skeletal muscle atrophy in heart failure. PloS one. 2012;7(8):e41701.