Effect of Long-Term Dietary Restriction on Myocardial Apoptosis

Document Type : Original Article (s)

Authors

1 Associate Professor, Department of Exercise Physiology, School of Physical Education and Sport Sciences, University of Tabriz, Tabriz, Iran

2 PhD Student, Department of Exercise Physiology, School of Physical Education and Sport Sciences, University of Tabriz, Tabriz, Iran

3 Assistant Professor, Department of Immunology, School of Medicine AND Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Background: Caloric or dietary restriction (DR) is a practical intervention for weight loss and increasing lifespan. However, the effects of long-term dietary restriction and signaling process of it on cell aging and apoptosis remain unclear, especially in sensitive somatic tissues such as myocardial. Therefore, the purpose of this study was investigating the effect of long-term dietary restriction on some indices of myocardial apoptosis in rats.Methods: This study was conducted with a two-group experimental design (animal model) for three months. Sixteen 3-month-old male Wistar14848 rats were selected and randomly divided into two groups of dietary restriction (n = 8; weight: 385.25 ± 29.6 g) and control (n = 8; weight: 231.25 ± 27.63 g). All animals in control group were fed ad libitum (0% of dietary restriction; 23.0 ± 2.16 g/day) and animals of dietary-restriction group had daily access to 50% of the intake of the ad libitum-fed control animals (-50% of dietary restriction; 11.5 ± 1.8 g/day). After 3 months, the hearts of rats were extracted and Bax, Bcl2 and caspase-3 mRNA, as important proteins in mitochondrial apoptosis pathway, were evaluated using real-time polymerase chain reaction (real-time PCR) method. Independent t-test was applied for statistical analysis of the data at the significant level of P < 0.05.Findings: The expressions of Bax and Bcl-2 genes in dietary-restriction group were unsignificantly higher than the control group (27.7% and 27.9%, respectively). In addition, caspase-3 expression and Bax/Bcl2 ratio in control group were unsignificantly higher than the dietary-restriction group (39.4% and 6.9%, respectively).Conclusion: In general, 3-month dietary restriction (-50%) did not affect myocardial apoptosis. However, it likely seems that dietary restriction alleviates myocardial apoptosis via increasing Bcl-2 and decreasing caspase-3.

Keywords


  1. Favaloro B, Allocati N, Graziano V, Di Ilio C, De Laurenzi V. Role of apoptosis in disease. Aging (Albany NY) 2012; 4(5): 330-49.
  2. Kwak HB. Effects of aging and exercise training on apoptosis in the heart. J Exerc Rehabil 2013; 9(2): 212-9.
  3. Lee Y, Min K, Talbert EE, Kavazis AN, Smuder AJ, Willis WT, et al. Exercise protects cardiac mitochondria against ischemia-reperfusion injury. Med Sci Sports Exerc 2012; 44(3): 397-405.
  4. Hashemi M, Kroczak TJ. Apoptosis and autoimmune disease. Antiinflamm Antiallergy Agents Med Chem 2005; 4(4): 429-37.
  5. 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 (1985) 2008; 105(6): 1934-43.
  6. Niemann B, Chen Y, Issa H, Silber RE, Rohrbach S. Caloric restriction delays cardiac ageing in rats: role of mitochondria. Cardiovasc Res 2010; 88(2): 267-76.
  7. Patel BP, Safdar A, Raha S, Tarnopolsky MA, Hamadeh MJ. Caloric restriction shortens lifespan through an increase in lipid peroxidation, inflammation and apoptosis in the G93A mouse, an animal model of ALS. PLoS One 2010; 5(2): e9386.
  8. Tejero-Taldo MI, Chmielinska JJ, Weglicki WB. Chronic dietary Mg2+ deficiency induces cardiac apoptosis in the rat heart. Magnes Res 2007; 20(3): 208-12.
  9. Selman C, Gredilla R, Phaneuf S, Kendaiah S, Barja G, Leeuwenburgh C. Short-term caloric restriction and regulatory proteins of apoptosis in heart, skeletal muscle and kidney of Fischer 344 rats. Biogerontology 2003; 4(3): 141-7.
  10. Gredilla R, Sanz A, Lopez-Torres M, Barja G. Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart. FASEB J 2001; 15(9): 1589-91.
  11. Boengler K, Schulz R, Heusch G. Loss of cardioprotection with ageing. Cardiovasc Res 2009; 83(2): 247-61.
  12. Hofer T, Servais S, Seo AY, Marzetti E, Hiona A, Upadhyay SJ, et al. Bioenergetics and permeability transition pore opening in heart subsarcolemmal and interfibrillar mitochondria: effects of aging and lifelong calorie restriction. Mech Ageing Dev 2009; 130(5): 297-307.
  13. Kumar D, Lou H, Singal PK. Oxidative stress and apoptosis in heart dysfunction. Herz 2002; 27(7): 662-8.
  14. Dirks AJ, Leeuwenburgh C. Tumor necrosis factor alpha signaling in skeletal muscle: effects of age and caloric restriction. J Nutr Biochem 2006; 17(8): 501-8.
  15. Li SY, Du M, Dolence EK, Fang CX, Mayer GE, Ceylan-Isik AF, et al. Aging induces cardiac diastolic dysfunction, oxidative stress, accumulation of advanced glycation endproducts and protein modification. Aging Cell 2005; 4(2): 57-64.
  16. Tsujita Y, Muraski J, Shiraishi I, Kato T, Kajstura J, Anversa P, et al. Nuclear targeting of Akt antagonizes aspects of cardiomyocyte hypertrophy. Proc Natl Acad Sci U S A 2006; 103(32): 11946-51.
  17. Marzetti E, Wohlgemuth SE, Anton SD, Bernabei R, Carter CS, Leeuwenburgh C. Cellular mechanisms of cardioprotection by calorie restriction: state of the science and future perspectives. Clin Geriatr Med 2009; 25(4): 715-32, ix.
  18. Speakman JR, Mitchell SE. Caloric restriction. Mol Aspects Med 2011; 32(3): 159-221.
  19. Dhahbi JM, Tsuchiya T, Kim HJ, Mote PL, Spindler SR. Gene expression and physiologic responses of the heart to the initiation and withdrawal of caloric restriction. J Gerontol A Biol Sci Med Sci 2006; 61(3): 218-31.
  20. Desport JC, Preux PM, Truong TC, Vallat JM, Sautereau D, Couratier P. Nutritional status is a prognostic factor for survival in ALS patients. Neurology 1999; 53(5): 1059-63.
  21. Kasarskis EJ, Berryman S, Vanderleest JG, Schneider AR, McClain CJ. Nutritional status of patients with amyotrophic lateral sclerosis: relation to the proximity of death. Am J Clin Nutr 1996; 63(1): 130-7.
  22. James SJ, Muskhelishvili L, Gaylor DW, Turturro A, Hart R. Upregulation of apoptosis with dietary restriction: implications for carcinogenesis and aging. Environ Health Perspect 1998; 106(Suppl 1): 307-12.
  23. Dalla LL, Ravara B, Volterrani M, Gobbo V, Della BM, Angelini A, et al. Beneficial effects of GH/IGF-1 on skeletal muscle atrophy and function in experimental heart failure. Am J Physiol Cell Physiol 2004; 286(1): C138-C144.
  24. Beurel E, Jope RS. The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways. Prog Neurobiol 2006; 79(4): 173-89.
  25. Pecina-Slaus N. Wnt signal transduction pathway and apoptosis: a review. Cancer Cell Int 2010; 10: 22.
  26. Whelan RS, Kaplinskiy V, Kitsis RN. Cell death in the pathogenesis of heart disease: mechanisms and significance. Annu Rev Physiol 2010; 72: 19-44.