Effects of Two Months of High Intensity Interval Training and Caffeine Supplementation on the Expression of Beclin-1 and Bcl-2 Proteins in the Myocardium of Type 2 Male Diabetic Rats

Document Type : Research Paper I Open Access I Released under (CC BY-NC 4.0) license

Authors

1 Associate professor, Department of Biological Sciences in Sport and Health, Shahid Beheshti University, Tehran, Iran

2 Ph.D, Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tabriz, Tabriz, Iran

3 Associate professor, Department of Exercise Physiology, School of Physical Education and Sport Sciences, University of Tabriz, Tabriz, Iran

4 Assistant professor, Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

5 Department of Exercise Physiology, Factulty of Physical Education and Sport Sciences, University of Tabriz, Tabriz, Iran

Abstract

Aim: Inhibitory and activating mechanisms of interventions such as high intensity interval training and caffeine administration on major pathways of programmed cell death (apoptosis and autophagy) are not well understood. The aim of present study was to evaluate the effects of high-intensity interval training along with caffeine administration on Beclin-1 and Bcl-2 proteins expression in myocardium muscle of type 2 diabetic male rats. Methods: In the present experimental study, 50 male white Wistar rats with an age range of 2-3 months were randomly divided into 5 groups of 10 rats in each group: Healthy control (C), Diabetic control (D), Diabetic with Training (D+T), Diabetic with Caffeine treatment (D+CA), Diabetic with Training and Caffeine treatment (D+T+CA). Western blot analysis was used to evaluate the cardiac muscle proteins (Bcl-2/Beclin-1). Results: The protein expression level of Beclin-1 was more than the C group, in D group; 201%, D+CA group; 215% and in D+CA+T group; 199% in compared to B-Actin (P=0.001). The Bcl-2 protein expression level in the experimental groups were significantly lower in comparison to the C group (P=0.001, F=73.83). As the expression level of this protein was significantly lower at around 37% in the D group compared to the C group (P=0.001). Whereas the Bcl-2 protein expression levels was significantly lower in the D+CA group and D+T+CA group compared to the C group at about 64 and 70 percent, respectively (P=0.001). Conclusion: The results indicate that performed high-intensity interval training is effective in modulating the overexpression of Beclin-1 autophagic index and improving expression of Bcl-2 anti-apoptotic index. However, caffeine supplementation alone and along with high-intensity interval training were not effective in modulating of autophagic protein and improving anti-apoptotic protein.

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This is an open access article distributed under the following Creative Commons license: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

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    1. Dorn, G.W., Mechanisms of non-apoptotic programmed cell death in diabetes and heart failure. Cell Cycle, 2010; 9(17): p. 3442-3448.
    2. Rubinstein, A.D. and A. Kimchi, Life in the balance–a mechanistic view of the crosstalk between autophagy and apoptosis. Journal of Cell Science, 2012; 125(22): p. 5259-5268.
    3. Nikoletopoulou, V., et al., Crosstalk between apoptosis, necrosis and autophagy. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research,2013; 1833(12): p. 3448-3459.
    4. Marquez, R.T. and L. Xu, Bcl-2: Beclin 1 complex: multiple,mechanisms regulating autophagy/apoptosis toggle switch. American Journal of Cancer Research, 2012; 2(2): p. 214.
    5. Murase, H., et al., Inhibition of DPP-4 reduces acute mortality after myocardial infarction with restoration of autophagic response in type 2 diabetic rats. Cardiovascular Diabetology, 2015; 14(1): p. 1-16.
    6. Xu, K., et al., Resveratrol modulates apoptosis and autophagy induced by high glucose and palmitate in cardiac cells. Cellular Physiology and Biochemistry, 2018; 46(5): p. 2031-2040.
    7. Zarghami Kamaneh A, Pashaei Z. The Effect of Medium- And High- Dose of Caffeine (1,3,7-Trimethylxanthine) Intake on Cardiovascular Factors Response at Baseline and Following One-Bout Aerobic Exercise. Journal of Applied Health Studies in Sport Physiology. 2019; 6(2):25-31.
    8. Li, Y.-F., et al., Caffeine protects skin from oxidative stress-induced senescence through the activation of autophagy. Theranostics. 2018; 8(20): p. 5713-21.
    9. Zarghami-Khameneh A, Jafari A. The effect of different doses of caffeine and a single bout of resistant-exhaustive exercise on muscle damage indices in male volleyball players. Feyz: (Journal of Kashan University of Medical Sciences). 2014; 18(3): p. 220-228.[In Persian]
    10. Saiki, S., et al., Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. Autophagy. 2011; 7(2): p. 176-187.
    11. Li, A. Low concentration of caffeine inhibits cell viability, migration and invasion, and induces cell apoptosis of B16F10 melanoma cells. International Journal of Clinical and Experimental Pathology. 2016; 9(11): p. 11206-11213.
    12. Nakaso, K., S. Ito, and K. Nakashima, Caffeine activates the PI3K/Akt pathway and prevents apoptotic cell death in a Parkinson's disease model of SH-SY5Y cells. Neuroscience Letters. 2008; 432(2): p. 146-150.
    13. He, C., et al., Dissociation of Bcl-2–Beclin1 complex by activated AMPK enhances cardiac autophagy and protects against cardiomyocyte apoptosis in diabetes. Journal of Diabetes. 2013; 62(4): p. 1270-1281.
    14. Weng, T.-P., et al., Effects of interval and continuous exercise training on CD4 lymphocyte apoptotic and autophagic responses to hypoxic stress in sedentary men. PLOS ONE. 2013; 8(11): p. e80248.

    15.Dadashzadeh A, Poozesh Jadidi R. Effect of HIIT and curcumin consumption on serum troponin I and creatine kinase levels in isopretrenol-treated male mice. Journal of Applied Health Studies in Sport Physiology. 2021; 8(1):44-53.

    16.Ebadi B, Damirchi A, Alamdari K, Darbandi-Azar A, Naderi N. Cardiomyocyte mitochondrial dynamics in health and disease and the role of exercise training: A brief review. Research in Cardiovascular Medicine.  2018; 7(3):107-15.

    17.Moieni A, Hosseini SA. Effect of Resistance Training Combined with Curcumin Supplementation on Expression of Regulatory Genes Related to Myocardial Remodeling in Obese Rats. Journal of Applied Health Studies in Sport Physiology. 2020; 7(2):45-52.

    18.Majidi A, Poozesh Jadidi R, Nourazar MAR, Bashiri J, Azali Alamdari KJSP. Effects of Aerobic Training and Curcumin Supplementation on Cardiomyocyte Apoptosis and MiRNAs Expression in Rats Exposed to Arsenic. Sport Physiology. 2020; 12(48):39-60.

    19.PouzeshJadidi G, Seifi-Skishahr F, Bolboli L, Azali Alamdari K, Pourrahim Ghouroghch A. Effect of high intensity interval training and curcumin supplementation on left ventriclular miR-133 and miR-1 gene expression levels in isoproterenol induced myocardial infarction rat model. Journal of Practical Studies of Biosciences in Sport. 2021; 4337.1638.

    1. Sasidharan, S.R., et al. An experimental approach for selecting appropriate rodent diets for research studies on metabolic disorders. BioMed Research International. 2013; p. 752870.

    21.Baydas G, Nedzvetskii VS, Nerush PA, Kirichenko SV, Yoldas T. Altered expression of NCAM in hippocampus and cortex may underlie memory and learning deficits in rats with streptozotocin-induced diabetes mellitus. Life Sciences. 2003; 29;73(15):1907-16.

    1. Sinha, R.A., et al., Caffeine stimulates hepatic lipid metabolism by the autophagy lysosomal pathway in mice. Hepatology. 2014; 59(4): p. 1366-1380.
    2. Asgari Hazaveh, D., S. Riyahi Malayeri, S. Babaei. Effect of eight weeks high intensity interval training and medium intensity interval training and aloe vera intake on serum vaspin and insulin resistance in diabetic male Rats. Journal of Arak University Medical Sciences. 2018;20(11): p. 67-75. [In Persian]
    3. Farhadi, H., et al. Effects of aerobic training and hypoxia on expression angiogenic factors in cardiac male Wistar rats. Journal of Sports Science. 2016; 2(16): p. 70-9.
    4. Li, S., et al., Excessive autophagy activation and increased apoptosis are associated with palmitic acid-induced cardiomyocyte insulin resistance. Journal of Diabetes Research. 2017:ID 2376893.
    5. He, C., et al., Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature. 2012; 481(7382): p. 511-515.
    6. Møller, A.B., et al., Altered gene expression and repressed markers of autophagy in skeletal muscle of insulin resistant patients with type 2 diabetes. Scientific Reports. 2017; 7(1): p. 1-11.
    7. Flusberg, D.A. and P.K. Sorger, Surviving apoptosis: life–death signaling in single cells. Trends in Cell Biology. 2015; 25(8): p. 446-458.
    8. Pitaksalee, R., et al., Autophagy inhibition by caffeine increases toxicity of methamphetamine in SH-SY5Y neuroblastoma cell line. Neurological Research. 2015; 27(4): p. 421-429.
    9. Hasani, S. and M. Habibian, The effect of regular high-intensity interval exercise on some apoptotic factors in the brain tissue of old female rats. Feyz: (Journal of Kashan University of Medical Sciences). 2018; 22(2): p. 128-133. [In Persian]
    10. Mejías-Peña, Y., et al., Impact of resistance training on the autophagy-inflammation-apoptosis crosstalk in elderly subjects. Aging. 2017; 9(2): p. 408.
    11. Lu, K., et al., 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. Molecular Medicine Reports. 2015; 12(2): p. 2374-2382.
    12. Lu, P.-Z., C.-Y. Lai, and W.-H. Chan, Caffeine induces cell death via activation of apoptotic signal and inactivation of survival signal in human osteoblasts. International Journal of Molecular Sciences. 2008; 9(5): p. 698-718.
    13. Chen, J.-C., Y.-C. Chan, and J.-H. Hwang, Effects of tetrandrine and caffeine on cell viability and expression of mammalian target of rapamycin, phosphatase and tensin homolog, histone deacetylase 1, and histone acetyltransferase in glioma cells. Tzu Chi Medical Journal. 2015; 27(2): p. 74-78.
    14. Mathew, T., et al., Caffeine promotes autophagy in skeletal muscle cells by increasing the calcium-dependent activation of AMP-activated protein kinase. Biochemical and Biophysical Research Communications. 2014; 453(3): p. 411-418.