Expression of the Mir-133 and Bcl-2 could be affected by swimming training in the heart of ovariectomized rats

Document Type : Original Article


1 Department of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran

2 Department of Histology & Embryology, Tabriz University of Medical Sciences, Tabriz, Iran

3 Department of Physiology, Tabriz Branch, Islamic Azad University, Tabriz, Iran

4 Tabriz University of Medical Sciences, Tabriz, Iran

5 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran


Objective(s): The beneficial and more potent role of exercise to prevent heart apoptosis in ovariectomized rats has been known. The aim of this study was to examine the effects of swimming training on cardiac expression of Bcl-2, and Mir-133 levels and glycogen changes in the myocyte.
Materials and Methods: Forty animals were separated into four groups as control, sham, ovariectomy (OVX) and ovariectomized group with 8 weeks swimming training (OVX.E). Training effects were evaluated by measuring lipid profiles, Bcl-2 and Mir-133 expression levels in the cardiac tissue. Grafts were analyzed by reverse transcription–polymerase chain reaction for Bcl-2 mRNA and Mir-133 and by Western blot for Bcl-2 protein.
Results: Ovariectomy down-regulated Bcl-2 and Mir-133 expression levels in the cardiac tissue, and swimming training up-regulated their expression significantly (P<0.05).
Conclusion: Our results showed that regular exercise as a physical replacement therapy could prevent and improve the effects of estrogen deficiency in the cardia.


1. Shuster LT, Rhodes DJ, Gostout BS, Grossardt BR, Rocca WA. Premature menopause or early menopause: long-term health consequences. Maturitas 2010; 65:161-166.
2. Mahdavian M, Abbassian H. Major cardiovascular risk factors for menopausal and non-menopausal women compared with men of the same age in Mashhad, Iran. J Midwifery Reprod Health 2014; 2:136-142.
3. Kim JK, Levin ER. Estrogen signaling in the cardiovascular system. Nucl Recept Signal 2006; 4: e013.
4. Hsu CC, Ou HC, Lee SD. Effects of exercise training on cardiac mitochondrial apoptosis in ovariectomized rats. FASEB J 2010; 24:601-605.
5. Liou CM, Yang AL, Kuo CH, Tin H, Huang CY, Lee SD. Effects of 17beta‐estradiol on cardiac apoptosis in ovariectomized rats. Cell Biochem Funct 2010; 28:521-528.
6.   Bluming AZ, Tavris C. Hormone replacement therapy: real concerns and false alarms. Cancer J 2009; 15:93-104.
7.   Chen CL, Weiss NS, Newcomb P, Barlow W, White E. Hormone replacement therapy in relation to breast cancer. Jama 2002; 287:734-741.
8. Mosca L, Collins P, Herrington DM, Mendelsohn ME, Pasternak RC, Robertson RM, et al. Hormone replacement therapy and cardiovascular disease a statement for healthcare professionals from the American Heart Association. Circulation 2001; 104:499-503.
9. Ososki AL, Kennelly EJ. Phytoestrogens: a review of the present state of research. Phytother Res 2003; 17:845-869.
10. Neves VJ, Fernandes T, Roque FR, Soci UPR, Melo SFS, de Oliveira EM. Exercise training in hypertension: Role of microRNAs. World J Cardiol 2014; 6:713.
11. Maillet M, van Berlo JH, Molkentin JD. Molecular basis of physiological heart growth: fundamental concepts and new players. Nat Rev Mol Cell Biol 2013; 14:38-48.
12. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004; 5:522-531.
13. Small EM, Frost RJ, Olson EN. MicroRNAs add a new dimension to cardiovascular disease. Circulation 2010; 121:1022-1032.
14. Wang N, Sun LY, Zhang S-C, Wei R, Xie F, Liu J, et al. MicroRNA-23a participates in estrogen deficiency induced gap junction remodeling of rats by targeting GJA1. Int J Biol Sci 2015; 11:390.
15. Abdellatif M. The role of microRNA-133 in cardiac hypertrophy uncovered. Circul Res 2010; 106:16-18.
16. Wang H, Li J, Chi H, Zhang F, Zhu X, Cai J, et al. MicroRNA‐181c targets Bcl‐2 and regulates mitochondrial morphology in myocardial cells. J Cell Mol Med 2015; 19:2084-2097.
17. Irigoyen M-C, Paulini J, Flores LJ, Flues K, Bertagnolli M, Moreira ED, et al. Exercise training improves baroreflex sensitivity associated with oxidative stress reduction in ovariectomized rats. Hypertension 2005; 46:998-1003.
18. Da Silva Jr ND, Fernandes T, Soci U, Monteiro A, Phillips MI, de Oliveira EM. Swimming training in rats increases cardiac MicroRNA-126 expression and angiogenesis. Med Sci Sports Exerc 2012; 44:1453-1462.
19. Lv H, Sun Y, Zhang Y. MiR-133 is involved in estrogen deficiency-induced osteoporosis through modulating osteogenic differentiation of mesenchymal stem cells. Med Sci Monit 2015; 21:1527-1534.
20. Klinge CM. Estrogen regulation of microRNA expression. Curr Genom 2009; 10:169.
21. Kataoka M, Wang D-Z. Non-coding RNAs including miRNAs and lncRNAs in cardiovascular biology and disease. Cells 2014; 3:883-898.
22. Boštjančič E, Zidar N, Štajer D, Glavač D. MicroRNAs miR-1, miR-133a, miR-133b and miR-208 are dysregulated in human myocardial infarction. Cardiology 2010; 115:163-169.
23. Zhao H, Li M, Li L, Yang X, Lan G, Zhang Y. MiR-133b is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation, migration and invasion, and promotes apoptosis. PLoS One 2013; 8:e83571.
24. Care A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med 2007; 13:613-618.
25. He B, Xiao J, Ren AJ, Zhang YF, Zhang H, Chen M, et al. Role of miR-1 and miR-133a in myocardial ischemic postconditioning. J Biomed Sci 2011; 18:22.
26. Xu C, Lu Y, Pan Z, Chu W, Luo X, Lin H, et al. The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes. J Cell Sci 2007; 120:3045-3052.
27. Mitchelson KR, Qin WY. Roles of the canonical myomiRs miR-1,-133 and-206 in cell development and disease. World J Biol Chem 2015; 6:162.
28. Xiao-Ming Y. Signal transduction mediated by Bid, a pro-death Bcl-2 family proteins, connects the death receptor and mitochondria apoptosis pathways. Cell Res 2000; 10:161-167.
29. Thomadaki H, Scorilas A. BCL2 family of apoptosis-related genes: functions and clinical implications in cancer. Crit Rev Clin Lab Sci 2006; 43:1-67.
30. Pasiakos SM, McClung JP. miRNA analysis for the assessment of exercise and amino acid effects on human skeletal muscle. Adv Nutr 2013; 4:412-417.
31. Wang N, Zhou Z, Liao X, Zhang T. Role of microRNAs in cardiac hypertrophy and heart failure. IUBMB life 2009; 61:566-571.
32. Cheng SM, Ho TJ, Yang AL, Chen IJ, Kao CL, Wu FN, et al. Exercise training enhances cardiac IGFI-R/PI3K/Akt and Bcl-2 family associated pro-survival pathways in streptozotocin-induced diabetic rats. Int J Cardiol 2013; 167:478-485.
33. Huang CY, Yang AL, Lin YM, Wu FN, Lin JA, Chan YS, et al. Anti-apoptotic and pro-survival effects of exercise training on hypertensive hearts. J Appl Physiol 2012; 12:883-891.