Effect of high-intensity interval training on expression of pro and anti-apoptotic genes in myocard tissue of aged male C57BL/6 mice

Soori, Rahman; Zare Shahneh, Maryam; Choubineh, Sirus; Ramezankhani, Azam

doi:10.48308/joeppa.2019.98930

Effect of high-intensity interval training on expression of pro and anti-apoptotic genes in myocard tissue of aged male C57BL/6 mice

Document Type : original article

Authors

Department of exercise physiology, Faculty of physical education and sport sciences, Tehran University, Tehran, Iran

10.48308/joeppa.2019.98930

Abstract

Purpose: Bax and BCL-2 genes are important genes that involve in the intrinsic pathway of apoptosis. Although the effects of interval and intensive exercises on the mechanisms involved in the gaining processes are less considered. So, the aim of the present study was to investigate the effect of high-intensity interval training on the expression of pro and anti-apoptotic genes (Bax and BCL-2) in myocard in aged male mice.
Methods: This experimental study was performed on twenty 24- months old C57BL/6 mice. Animals were randomly assigned to the control (n=10) and experimental groups (n=10). The experimental group performed high interval intensity training for four weeks (five sessions per week). At first, the interval training started at the intensity equal to 85 percent of maximum speed and in the continuation of interval training, 5 percent was added weekly and the last two weeks ended with 95 percent rate. Forty-eight hours after the last training session, myocardial muscle was removed. Bax and BCL-2 genes expression were investigated by SYBR-Green Real-time PCR analysis.
Results: The results of Real Time-PCR showed that the average relative expression of pro-apoptotic Bax gene was significantly lower in the experimental group than in the control group (0.618±0.022 vs. 1 unit; P<0.05). Also, the average relative expression of Anti-apoptotic Bcl2 gene expression was higher in the experimental group than in the control group (1.824±0.084 vs. 1 unit; P< 0.05).
Conclusion: The results showed that high-intensity interval training by modifying the expression of pro and anti-apoptotic genes (Bax and BCL-2) may be effective in reducing apoptosis in cardiac tissue of aged mice.

Keywords

References

1. Seo H, Park CH, Choi S, Kim W, Jeon BD, Ryu S. Effects of voluntary exercise on apoptosis and cortisol after chronic restraint stress in mice. J Exerc Nutrition Biochem. 2016; 20: 16-23.

2. Khan KH, Blanco-Codesido M, Molife LR. Cancer therapeutics: Targeting the apoptotic pathway. Crit Rev Oncol Hematol. 2014; 90: 200-219.

3. Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D'Orazi G. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY). 2016; 8: 603-619.

4. Tabas I, Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol 2011; 13: 184-190.

5. Parrish AB, Freel CD, Kornbluth S. Cellular mechanisms controlling caspase activation and function. Cold Spring Harb Perspect Biol. 2013; 5: 1-25.

6. Marzetti E, Privitera G, Simili V, Wohlgemuth SE, Aulisa L, Pahor M, Leeuwenburgh C. Multiple pathways to the same end: mechanisms of myonuclear apoptosis in sarcopenia of aging. Scientific World Journal. 2010; 10: 340-349.

7. Gross A. BCL-2 family proteins as regulators of mitochondria metabolism. Biochim Biophys Actaa. 2016; 1857(8): 1243-1246.

8. Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014; 15: 49-63.

9. Strait JB, Lakatta EG. Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin. 2012; 8: 143-164.

10. Kwak HB. Effects of aging and exercise training on apoptosis in the heart. J Exerc Rehabil. 2013; 9: 212-219.

11. Fannin J, Rice KM, Thulluri S, Arvapalli RK, Wehner P, Blough ER. The Effects of aging on indices of oxidative stress and apoptosis in the female fischer 344/Nnia X brown Norway/BiNia rat heart. Open Cardiovasc Med J. 2013; 7: 113-121.

12. Peterson JM, Bryner RW, Sindler A, Frisbee JC, Alway SE. Mitochondrial apoptotic signaling is elevated in cardiac but not skeletal muscle in the obese Zucker rat and is reduced with aerobic exercise. J Appl Physiol. 2008; 105: 1934-1943.

13. Lee SD, Shyu WC, Cheng IS, Kuo CH, Chan YS, Lin YM, Tasi CY, Tsai CH, Ho TJ, Huang CY. Effects of exercise training on cardiac apoptosis in obese rats. Nutr Metab Cardiovasc Dis. 2013; 23: 566-73.

14. Jafari A, Pourrazi H, Nikookheslat S, Baradaran B. Effect of exercise training on Bcl-2 and Bax gene expression in the rat heart. Gene Cell Tissue. 2015; 2: e32833.

15. Gibala MJ, Ballantyne C. High-intensity interval training: New insights. Sports Science Exchange. 2007; 20(2): 1-5.

16. Gibala MJ, Little JP, Macdonald MJ, Hawley JA. Physiological adaptations to low-volume, high-intensity interval training in health and disease. J Physiol. 2012; 590(5): 1077-1084.

17. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (Delta Delta C (T)) Method. Methods. 2001; 25(4): 402-408.

18. Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1alpha in human skeletal muscle. J Appl Physiol. 2009; 106: 929-934.

19. 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. Am J Physiol Endocrinol Metab. 2007; 293: E916-922.

20. Yuan Q, Chen Z, Santulli G, Gu L, Yang ZG, Yuan ZQ, Zhao YT, Xin HB, Deng KY, Wang SQ, Ji G. Functional role of Calstabin2 in age-related cardiac alterations. Sci Rep. 2014; 4: 1-9.

21. Lee BS, Kim SH, Jin T, Choi EY, Oh J, Park S, Lee SH, Chung JH, Kang SM. Protective effect of survivin in Doxorubicin-induced cell death in h9c2 cardiac myocytes. Korean Circ J. 2013; 43:400-407.

22. Kwak HB, Song W, Lawler JM. Exercise training attenuates age-induced elevation in Bax/Bcl-2 ratio, apoptosis, and remodeling in the rat heart. FASEB J. 2006; 20:791-793.

23. KoIG, Kim SE, Jee YS. Treadmill exercise alleviates aging-induced apoptosis in rat cardiac myocytes. Gerontology. 2013; 7: 152-157.

24. Huang CY, Lin YY, Hsu CC, Cheng SM, Shyu WC, Ting H Yang AL, Ho TJ, Lee SD. Antiapoptotic effect of exercise training on ovariectomized rat hearts. J Appl Physiol. 2016; 121: 457-465.

25. Wang Z, Liu D, Varin A, Nicolas V, Courilleau D, Mateo P, Caubere C, Rouet P, Gomez AM, Vandecasteele G, Fischmeister R, Brenner C. A cardiac mitochondrial cAMP signaling pathway regulates calcium accumulation, permeability transition and cell death. Cell Death Dis. 2016; 7: e2198.

26. Feng P, Li T, Guan Z, Franklin RB, Costello LC. The involvement of Bax in zinc-induced mitochondrial apoptogenesis in malignant prostate cells. Mol Cancer. 2008; 7: 1-6.

27. French JP, Hamilton KL, Quindry JC, Lee Y, Upchurch PA, Powers SK. Exercise-induced protection against myocardial apoptosis and necrosis: MnSOD, calcium-handling proteins, and calpain. FASEB J. 2008; 22: 2862-2871.

28. Cagnol S, Chambard JC. ERK and cell death: mechanisms of ERK-induced cell death-apoptosis, autophagy and senescence. FEBS J. 2010; 277: 2-21.

29. Lanneau D, Brunet M, Frisan E, Solary E, Fontenay M, Garrido C. Heat shock proteins: essential proteins for apoptosis regulation. J Cell Mol Med. 2008; 12: 743-761.

30. Trocoli A, Djavaheri-Mergny M. The complex interplay between autophagy and NF-κB signaling pathways in cancer cells. Am J Cancer Res. 2011; 1: 629-649.

31. Zhang X, Tang N, Hadden TJ, Rishi AK. Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta. 2011; 1813: 1978-1986.

32. Lai CH, Ho TJ, Kuo WW, Day CH, Pai PY, Chung LC, Liao PH, Lin FH, Wu ET, Huang CY. Exercise training enhanced SIRT1 longevity signaling replaces the IGF1 survival pathway to attenuate aging-induced rat heart apoptosis. Age (Dordr). 2014; 36: 1-13.

33. Siu PM, Bryner RW, Martyn JK, Alway SE. Apoptotic adaptations from exercise training in skeletal and cardiac muscles. FASEB J. 2004; 18: 1150-2.

34. PMID: 15132982 Xiong S, Mu T, Wang G, Jiang X. Mitochondria-mediated apoptosis in mammals. Protein Cell 2014; 5: 737-749.

35. Hardwick JM, Soane L. Multiple functions of BCL-2 family proteins. Cold Spring Harb Perspect Biol. 2013; 5: 1-22.

36. Bratton SB, Salvesen GS. Regulation of the Apaf-1-caspase-9 apoptosome. J Cell Sci. 2010; 123: 3209-3214.

37. Habibi P, Alihemmati AR, NourAzar AR, Yousefi H, Mortazavi S, Ahmadiasl N. Expression of the Mir‐133 and Bcl‐2 could be affected by swimming training in the heart of ovariectomized rats. IJBMS. 2016; 19: 381‐387.

38. Lu K, Wang L, Wang C, Yang Y, Hu D, Ding R. Effects of high-intensity interval versus continuous moderate-intensity aerobic exercise on apoptosis, oxidative stress and metabolism of the infarcted myocardium in a rat model. Mol Med Rep. 2015; 12(2): 2374-2382.