[Home ] [Archive]    
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
Main Menu
Home::
About Journal::
Editorial Board::
Articles Archive::
Indexing Databases::
To Authors::
To Reviewers::
Registration::
Submit Your Article::
Policies and Publication Ethics::
Archiving Policy::
Site Facilities::
Contact Us::
::
Google Scholar Metrics

Citation Indices from GS

AllSince 2019
Citations746606
h-index1110
i10-index1513
..
Search in website

Advanced Search
..
Receive site information
Enter your Email in the following box to receive the site news and information.
..
Registered in

AWT IMAGE

AWT IMAGE

..
:: Volume 10, Issue 4 (12-2023) ::
2023, 10(4): 54-66 Back to browse issues page
A Comparative Analysis of Two High-Intensity Interval Training (HIIT) Programs on PGC-1α, p53, and Citrate Synthase Protein Levels in Cardiomyocytes of Male Type 2 Diabetic Rats
Nadia Khayampour , Maghsoud Peeri , Mohammad Ali Azarbayjani
Department of Exercise Physiology, Physical Education Faculty, Central Tehran Branch, Islamic Azad University, Tehran, Iran , m.peeri@iauctb.ac.ir
Abstract:   (337 Views)
Introduction: This study investigates the impact of two high-intensity interval training (HIIT) programs on PGC-1α, p53, and citrate synthase (CS) proteins within cardiomyocytes of male type 2 diabetic rats, aiming to discern potential molecular mechanisms influencing cardiac health.
Material & Methods: Twenty-four male Wistar rats were randomly assigned to control (NC), diabetic control (DC), diabetic with type 1 HIIT (HIIT-1), and diabetic with type 2 HIIT (HIIT-2) groups. Streptozotocin (STZ) induced type 2 diabetes, excluding the NC group. A four-week HIIT intervention, six sessions per week, preceded the analysis of heart tissue for PGC-1α, p53, and CS protein levels. Statistical analysis employed GraphPad Prism software version 8 and one-way ANOVA (P < 0.05).
Results: Both HIIT-1 (p=0.004) and HIIT-2 (p=0.007) groups exhibited significantly elevated cardiac PGC-1α levels compared to DC. CS levels increased notably in HIIT-1 (p=0.001) and HIIT-2 (p<0.001), with HIIT-2 surpassing HIIT-1 significantly (p=0.010). Concurrently, p53 levels significantly decreased in both HIIT-1 (p=0.005) and HIIT-2 (p=0.001) groups compared to DC.
Conclusion: Exercise training (HIIT) positively influences cardiac metabolism, evident in PGC-1α and CS upregulation and p53 downregulation. While these findings provide valuable insights, further exploration is crucial for a comprehensive understanding of the underlying molecular mechanisms. This study advances our understanding of optimizing exercise interventions for improved cardiac health in type 2 diabetes.
Keywords: Exercise Therapy, Type 2 Diabetes Mellitus, Mitochondrial Diseases, PGC-1alpha, Tumor Suppressor Protein p53, Citrate (si)-Synthase
Full-Text [PDF 3694 kb]   (91 Downloads)    
Type of Study: Research | Subject: Physiology
Received: 2022/02/23 | Accepted: 2022/02/26 | Published: 2023/12/28
References
1. Doria A, Patti M-E, Kahn CR. The emerging genetic architecture of type 2 diabetes. Cell metabolism. 2008;8(3):186-200. doi: 10.1016/j.cmet.2008.08.006.
2. Artasensi A, Pedretti A, Vistoli G, Fumagalli L. Type 2 diabetes mellitus: a review of multi-target drugs. Molecules. 2020;25(8):1987. doi: 10.3390/molecules25081987.
3. Miki T, Yuda S, Kouzu H, Miura T. Diabetic cardiomyopathy: pathophysiology and clinical features. Heart failure reviews. 2013;18(2):149-66. doi: 10.1007/s10741-012-9313-3.
4. Rijzewijk LJ, van der Meer RW, Lamb HJ, de Jong HW, Lubberink M, Romijn JA, et al. Altered myocardial substrate metabolism and decreased diastolic function in nonischemic human diabetic cardiomyopathy: studies with cardiac positron emission tomography and magnetic resonance imaging. Journal of the American College of Cardiology. 2009;54(16):1524-32. doi: 10.1016/j.jacc.2009.04.074.
5. Khakdan S, Delfan M, Heydarpour Meymeh M, Kazerouni F, Ghaedi H, Shanaki M, et al. High-intensity interval training (HIIT) effectively enhances heart function via miR-195 dependent cardiomyopathy reduction in high-fat high-fructose diet-induced diabetic rats. Archives of physiology and biochemistry. 2020;126(3):250-7. doi: 10.1080/13813455.2018.1511599.
6. Bombicino SS, Iglesias DE, Mikusic IAR, D’Annunzio V, Gelpi RJ, Boveris A, et al. Diabetes impairs heart mitochondrial function without changes in resting cardiac performance. The international journal of biochemistry & cell biology. 2016; 81:335-45. doi: 10.1016/j.biocel.2016.09.018.
7. Wang CH, Wang CC, Wei YH. Mitochondrial dysfunction in insulin insensitivity: implication of mitochondrial role in type 2 diabetes. Annals of the New York Academy of Sciences. 2010;1201(1):157-65. doi: 10.1111/j.1749-6632.2010.05625. x.
8. Puigserver P, Spiegelman BM. Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α): transcriptional coactivator and metabolic regulator. Endocrine reviews. 2003;24(1):78-90. doi: 10.1210/er.2002-0012. doi: 10.3389/fcvm.2020.00002.
9. Oka S-i, Sabry AD, Cawley KM, Warren JS. Multiple levels of PGC-1α dysregulation in heart failure. Frontiers in Cardiovascular Medicine. 2020:2.
10. Fang W-j, Wang C-j, He Y, Zhou Y-l, Peng X-d, Liu S-k. Resveratrol alleviates diabetic cardiomyopathy in rats by improving mitochondrial function through PGC-1α deacetylation. Acta Pharmacologica Sinica. 2018;39(1):59-73. doi: 10.1038/aps.2017.50.
11. Villeneuve C, Guilbeau-Frugier C, Sicard P, Lairez O, Ordener C, Duparc T, et al. p53-PGC-1α pathway mediates oxidative mitochondrial damage and cardiomyocyte necrosis induced by monoamine oxidase-A upregulation: role in chronic left ventricular dysfunction in mice. Antioxidants & redox signaling. 2013;18(1):5-18. doi: 10.1089/ars.2011.4373.
12. Delfan M, Vahed A, Bishop DJ, Amadeh Juybari R, Laher I, Saeidi A, et al. Effects of two workload-matched high intensity interval training protocols on regulatory factors associated with mitochondrial biogenesis in the soleus muscle of diabetic rats. Frontiers in Physiology. 2022; 13:927969. doi: 10.3389/fphys.2022.927969.
13. Fujita T, Ishikawa Y. Apoptosis in Heart Failure–The Role of the β-Adrenergic Receptor-Mediated Signaling Pathway and p53-Mediated Signaling Pathway in the Apoptosis of Cardiomyocytes–. Circulation Journal. 2011;75(8):1811-8. doi: 10.1253/circj. cj-11-0025.
14. Men H, Cai H, Cheng Q, Zhou W, Wang X, Huang S, et al. The regulatory roles of p53 in cardiovascular health and disease. Cellular and Molecular Life Sciences. 2021;78(5):2001-18. doi: 10.1007/s00018-020-03694-6.
15. Vousden KH, Lane DP. p53 in health and disease. Nature reviews Molecular cell biology. 2007;8(4):275-83. doi: 10.1038/nrm2147.
16. Khayampour N, Peeri M, Azarbayjani MA, Delfan M. Effects of High Intensity Interval Training on the Gene Expression of PGC1-Α, CS and P-53 in the Cardiomyocyte of Male Obese Rats in Type 2 Diabetes. Journal of Shahid Sadoughi University of Medical Sciences. 2020. doi: 10.18502/ssu. v28i11.5222. doi: 10.18502/ssu. v28i11.5222.
17. Spina RJ, Chi M, Hopkins MG, Nemeth P, Lowry O, Holloszy J. Mitochondrial enzymes increase in muscle in response to 7-10 days of cycle exercise. Journal of applied physiology. 1996;80(6):2250-4. doi: 10.1152/jappl.1996.80.6.2250.
18. Heilbronn LK, Gan SK, Turner N, Campbell LV, Chisholm DJ. Markers of mitochondrial biogenesis and metabolism are lower in overweight and obese insulin-resistant subjects. The Journal of Clinical Endocrinology & Metabolism. 2007;92(4):1467-73. doi: 10.1210/jc.2006-2210.
19. Teixeira-Lemos E, Nunes S, Teixeira F, Reis F. Regular physical exercise training assists in preventing type 2 diabetes development: focus on its antioxidant and anti-inflammatory properties. Cardiovascular diabetology. 2011;10(1):1-15. doi: 10.1186/1475-2840-10-12.
20. Delfan M, Delphan M, Kordi MR, Ravasi AA, Safa M, Gorgani-Firuzjaee S, et al. High intensity interval training improves diabetic cardiomyopathy via miR-1 dependent suppression of cardiomyocyte apoptosis in diabetic rats. Journal of Diabetes & Metabolic Disorders. 2020; 19:145-52. doi: 10.1007/s40200-019-00485-0.
21. Mirakhori Z, Kordi MR, Alizadeh S, Anoosheh L, Amani Shalamzari S, Amini A, et al. The effect of aerobic training on plasma estradiol and mir-206 and erα expression in mice with breast cancer. Iranian Journal of Breast Diseases. 2015;7(4):23-32. doi: 20.1001.1.17359406.1393.7.4.3.7.
22. Akbari N, Peeri M, Azarbayjani MA, Delfan M. Comparison of the effect of 8 weeks of continuous and high intensity interval training on the gene expression of TIMP-2 and MMP-2 in male diabetic rats. Razi Journal of Medical Sciences. 2019;26(10):107-16. http://rjms.iums.ac.ir/article-1-5702-en.html.
23. Wang H, Bei Y, Lu Y, Sun W, Liu Q, Wang Y, et al. Exercise prevents cardiac injury and improves mitochondrial biogenesis in advanced diabetic cardiomyopathy with PGC-1α and Akt activation. Cellular physiology and biochemistry. 2015;35(6):2159-68. doi: 10.1159/000374021.
24. Ghafari S, Nazarali P, Razavi A, Delfan M. Effect of continuous aerobic training versus high intensity interval training on Resistin and insulin resistance in type 2 diabetic rats. Journal of Shahid Sadoughi University of Medical Sciences. 2019.
25. Winding KM, Munch GW, Iepsen UW, Van Hall G, Pedersen BK, Mortensen SP. The effect on glycaemic control of low‐volume high‐intensity interval training versus endurance training in individuals with type 2 diabetes. Diabetes, Obesity and Metabolism. 2018;20(5):1131-9. doi: 10.1111/dom.13198.
26. Rezaee N, Rahmani-Nia F, Delfan M, Ghahremani R. Exercise training and probiotic supplementation effects on skeletal muscle apoptosis prevention in type-Ι diabetic rats. Life Sciences. 2021; 285:119973. doi: 10.1016/j.lfs.2021.119973.
27. PITHON-CURI TNC. Aprogram Of Moderate Physical Training For Wistar Rats Based On Maximal Oxygen Consumption. J Strength Cond Res. 2007; 21(3):751-6. doi: 10.1519/R-20155.1.
28. Yan W, Zhang H, Liu P, Wang H, Liu J, Gao C, et al. Impaired mitochondrial biogenesis due to dysfunctional adiponectin-AMPK-PGC-1α signaling contributing to increased vulnerability in diabetic heart. Basic Res Cardiol. 2013; 108(3):1-15. doi: 10.1007/s00395-013-0329-1.
29. Zamora M, Pardo R, Villena JA. Pharmacological induction of mitochondrial biogenesis as a therapeutic strategy for the treatment of type 2 diabetes. Biochem Pharmacol. 2015; 98(1):16-28. doi: 10.1016/j.bcp.2015.06.032.
30. Hood DA. Mechanisms of exercise-induced mitochondrial biogenesis in skeletal muscle. Applied Physiology, Nutrition, and Metabolism. 2009;34(3):465-72.
31. Wang SY, Zhu S, Wu J, Zhang M, Xu Y, Xu W, et al. Exercise enhances cardiac function by improving mitochondrial dysfunction and maintaining energy homoeostasis in the development of diabetic cardiomyopathy. J Mol Med. 2020; 98(2):245-61. doi: 10.1007/s00109-019-01861-2.
32. Jia D, Hou L, Lv Y, Xi L, Tian Z. Postinfarction exercise training alleviates cardiac dysfunction and adverse remodeling via mitochondrial biogenesis and SIRT1/PGC‐1α/PI3K/Akt signaling. J Cell Physiol. 2019; 234(12):23705-18. doi: 10.1002/jcp.28939.
33. Tao L, Bei Y, Lin S, Zhang H, Zhou Y, Jiang J, et al. Exercise training protects against acute myocardial infarction via improving myocardial energy metabolism and mitochondrial biogenesis. Cell Physiol Biochem. 2015; 37(1):162-75. doi: 10.1159/000430342.
34. Zhang Y, Köhler K, Xu J, Lu D, Braun T, Schlitt A, et al. Inhibition of p53 after acute myocardial infarction: reduction of apoptosis is counteracted by disturbed scar formation and cardiac rupture. J Mol Cell Cardiol. 2011; 50(3):471-8. doi: 10.1016/j.yjmcc.2010.11.006.
35. Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A, Nakaoka M, et al. p53 promotes cardiac dysfunction in diabetic mellitus caused by excessive mitochondrial respiration-mediated reactive oxygen species generation and lipid accumulation. Circ Heart Fail. 2012; 5(1):106-15. doi: 10.1161/CIRCHEARTFAILURE.111.961565.
36. Gu J, Wang S, Guo H, Tan Y, Liang Y, Feng A, et al. Inhibition of p53 prevents diabetic cardiomyopathy by preventing early-stage apoptosis and cell senescence, reduced glycolysis, and impaired angiogenesis. Cell Death Dis. 2018; 9(2):1-17. doi: 10.1038/s41419-017-0093-5.
37. Al-Jarrah M, Ahmad MB, Maayah M, Al-Khatib A. Effect of exercise training on the expression of p53 and iNOS in the cardiac muscle of type I diabetic rats. J Clin Endocrinol Metab. 2012; 2(4-5):176-80. doi: 10.4021/jem123e.
38. Qi Z, He J, Zhang Y, Shao Y, Ding S. Exercise training attenuates oxidative stress and decreases p53 protein content in skeletal muscle of type 2 diabetic Goto-Kakizaki rats. Free Radic Biol Med. 2011; 50(7):794-800. doi: 10.1016/j.freeradbiomed.2010.12.022.
39. Mak TW, Hauck L, Grothe D, Billia F. p53 regulates the cardiac transcriptome. Proc Natl Acad Sci. 2017; 114(9):2331-6. doi: 10.1073/pnas.1621436114.
40. Siu PM, Donley DA, Bryner RW, Alway SE. Citrate synthase expression and enzyme activity after endurance training in cardiac and skeletal muscles. J Appl Physiol. 2003;94(2):555-60. doi: 10.1152/japplphysiol.00821.2002.
41. Leek BT, Mudaliar SR, Henry R, Mathieu-Costello O, Richardson RS. Effect of acute exercise on citrate synthase activity in untrained and trained human skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2001; 280(2): R441-R7. doi: 10.1152/ajpregu.2001.280.2. R441.
42. Vigelsø A, Andersen NB, Dela F. The relationship between skeletal muscle mitochondrial citrate synthase activity and whole-body oxygen uptake adaptations in response to exercise training. Int J Physiol Pathophysiol Pharmacol. 2014; 6(2):84-101. PMID: 25057335.
Send email to the article author

Add your comments about this article
Your username or Email:

CAPTCHA


XML     Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Khayampour N, Peeri M, Azarbayjani M A. A Comparative Analysis of Two High-Intensity Interval Training (HIIT) Programs on PGC-1α, p53, and Citrate Synthase Protein Levels in Cardiomyocytes of Male Type 2 Diabetic Rats. Journal of Basic Research in Medical Sciences 2023; 10 (4) :54-66
URL: http://jbrms.medilam.ac.ir/article-1-671-en.html


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 10, Issue 4 (12-2023) Back to browse issues page
مجله ی تحقیقات پایه در علوم پزشکی Journal of Basic Research in Medical Sciences
Persian site map - English site map - Created in 0.17 seconds with 41 queries by YEKTAWEB 4654