Volume 23, Issue 6 (Feb - Mar 2020)                   2020, 23(6): 484-493 | Back to browse issues page

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Jokar M, Sherafati Moghadam M, Daryanoosh F. The Effect of an 8-Week Endurance Training Program on the Content of FOXO3a and Beclin-1 Proteins in Heart Muscle of Rats With Type 2 Diabetes. Journal of Inflammatory Diseases. 2020; 23 (6) :484-493
URL: http://journal.qums.ac.ir/article-1-2923-en.html
1- Department Exercise Physiology, Faculty of Physical Education and Sport Sciences, Kharazmi University, Tehran, Iran.
2- Department of Pure and Basic Science, Hashtgerd Branch, Islamic Azad University, Alborz, Iran. , m.sherafati@hiau.ac.ir
3- Department of Exercise Physiology, School of Education and Psychology, University of Shiraz, Shiraz, Iran.
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Extended Abstract
1. Introduction

Diabetic cardiomyopathy is one of the most important complications of type 2 diabetes, which is known as a specific disease of the heart muscle [5]. Diabetic cardiomyopathy predisposes cardiac muscle cells to cell death and eventually causes muscle contraction [6]. Autophagy is a process to maintain cellular survival through which cytoplasmic components are destroyed. Autophagy is responsible for recycling macromolecules to generate energy and renewal within the cell [8]. Defects in autophagy process can cause numerous diseases, including diabetes, cancer, neurological problems, infection, and aging [9]. Forkhead Box class O (FOXO) family member proteins such as FOXO3a are involved in autophagy promotion. FOXO3a, by activating proteins such as Beclin-1, can cause autophagy and apoptosis. Thus, this interaction may be an important mechanism in regulation of both autophagy and apoptosis [11]. By regulating autophagy and apoptosis, Beclin-1 protein plays an important role as a "cell death pathway" [13].
Exercise is one of the important ways for the prevention and treatment of heart disease. It has a positive effect on the physiology and morphology of the heart tissue [14]. Cellular adaptation to physical activity can be related to cellular and molecular factors and cause cardiac growth by inducing hypertrophy and cardiomyocyte remodeling [15]. Autophagy during exercise can limit tissue damage, restore tissue integrity, terminate inflammatory responses, and generate direct signals for adaptation [16].There are limited number of studies on the cellular mechanism, autophagy, especially the FOXO3a and Beclin-1 proteins pathway, in patients with type 2 diabetic who are susceptible to cardiomyopathy and myocyte necrosis. The aim of this study was to investigate the effect of a 8-week endurance training program on the content of FOXO3a and Beclin-1 proteins in heart muscle tissue of Sprague-Dawley rats with type 2 diabetes.
2. Materials and Methods
The present study is an experimental/fundamental research conducted on twelve male 2-month-old Sprague Dawley rats with a mean weight of 270±20 g. To induce the type 2 diabetes in rats, streptozotocin was injected intraperitoneally once at a dose of 60 mg/kg body weight, after 15 minutes of nicotinamide injection at a dose of 110 mg/kg body weight [19]. To ensure that the animals were diabetic, their blood glucose level was measured 72 hours after injection, and the glucose level of 130-260 mg/dl was considered as diagnostic criterion for type 2 diabetes [20]. One week after induction of diabetes, the rats were randomly divided into two groups of diabetic- exercise (n=6) and diabetic control (n=6).
The exercise group received intervention for 8 weeks, 4 sessions per week. Each session, they ran for 42 minutes on a treadmill, which included 6-min warm up (at a speed of 10-12 m/min), 30-min endurance training (at an intensity of about 50-70% of maximum heart rate and a speed of 10-30 m/min) and 6-min cooling down (at a speed of 10-12 m/min). The treadmill incline was at zero degree and did not change for 8 weeks [21]. During this period, the control group received no any training program. The study rats did not have any insulin therapy during the study period. To eliminate the acute effects of exercise and the uncontrollable stressors in subjects during the exercise intervention, they were anesthetized based on ethical principles 24 hours after the last training session by intraperitoneal injection of Ketamine/Xylazine combination. Then, the heart muscle tissue was removed from the body, washed in physiological saline, and immediately frozen with nitrogen and kept at 80°C for future analysis.
The variables of research were measured using western blot method. Proteins were measured by a chemical reaction (Chemiluminescence) and visualized using x-ray film. Densitometric analysis was conducted in ImageJ v. software, and the results were normalized to intrinsic control protein (β-actin) in multiples control groups [24]. For statistical analysis in SPSS V. 19 software, first the Kolmogorov-Smirnov test (KS) was used to determine the normality of data distribution. Since the distribution was normal, independent t-test was used for comparing the study groups. The significance level was set as P≤0.05.
3. Results
The results showed that after 8 weeks of endurance training, there was no significant change in FOXO3a protein content between study groups (P=0.12) (Figure 1, A and B). The endurance training intervention could not significantly decrease the Beclin-1 protein content in cardiac muscle tissue (P=0.34) among study groups (Figure 2, A and B).
4. Discussion
Marfe et al. (2012) showed a decrease in FOXO3a transcription after a prolonged period of physical activity, leading to helplessness in heart and skeletal muscle tissue rats [17]. Brandt et al. (2018) showed that moderate-intensity cycling training significantly increased Beclin-1 protein content immediately and after exercise compared its content before exercise [18]. These are consistent with our results. Overall, the results of this study showed that endurance training can not significantly change the content of FOXO3a and Beclin-1 proteins. Therefore, it seems that endurance training may not affect autophagy in the heart muscle of type 2 diabetic subjects. It is necessary to pay attention to the characteristics of exercise (such as intensity, duration and type) to optimally modify the autophagy signaling in the heart muscle. Further studies should be conducted in this area.
Ethical Considerations
Compliance with ethical guidelines
This study was obtained an ethical approval from Shiraz University of Medical Sciences (Code: IR.SUMS.REC.1396.S1062).

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Authors' contributions
Writing: All authors; Resources & validation: Masoud Jokar; Editing and project administration: Mohammad Sharafati Moghadam; Data analysis and Methodology: Farhad Daryanoosh.
Conflicts of interest
The authors declared no conflict of interest.
Type of Study: Research | Subject: physical education

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