The Effect of Six Weeks of Aerobic Training on Expression of Endoplasmic Reticulum Stress Genes (X-box Binding Protein-1 and Eukaryotic Initiation Factor 2α) in the Heart Tissue of Male Rats with Streptozotocin (STZ)-Induced Diabetes

Document Type : Original Article (s)

Authors

1 Instructor, Department of Sport Physiology, School of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

2 PhD in Sport Physiology, School of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

Abstract

Background: The aim of this study was to investigate the effect of six weeks of aerobic training on expression of endoplasmic reticulum stress genes [X-box binding protein-1 (XBP1) and eukaryotic initiation factor 2α (eIF2α)] in the heart tissue of male rats with streptozotocin (STZ)-induced diabetes.Methods: Twenty male rats with the mean weight of 204.0 ± 11.3 grams were randomly divided into four groups including of healthy control, healthy exercise, diabetic control, and diabetic training. They became diabetic by intraperitoneal injection of STZ (50 mg/kg). After confirmation of induction of diabetes by measuring fasting blood glucose level with glucometer, aerobic training program was performed with an average intensity for 30 minutes at a speed of 18 meters per minute, 5 days a week for 6 weeks. The expression of endoplasmic reticulum stress genes (XBP1 and eIF2α) was measured using real-time polymerase chain reaction (RT-PCR) technique. One-way analysis of variance and Tukey's post hoc test were used for statistical analysis.Findings: The expression of endoplasmic reticulum stress genes (XBP1 and eIF2α) in heart tissue in diabetic rats was significantly higher than the healthy control group. After 6 weeks of aerobic exercise protocol, the expression of these genes in heart tissue was significantly lower in the diabetic group of exercise, healthy exercise, and healthy control than the diabetic control group.Conclusion: The results of the present study showed that by reducing endoplasmic reticulum stress factors in the heart of male rats with diabetes, aerobic training can be useful as a preventive and non-pharmacological factor in the treatment of patients with diabetes.

Keywords


  1. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract 2019; 157: 107843.
  2. Gray SP, Cooper ME. Diabetic nephropathy in 2010: Alleviating the burden of diabetic nephropathy. Nat Rev Nephrol 2011; 7(2): 71-3.
  3. Liu HF, Zhang HJ, Hu QX, Liu XY, Wang ZQ, Fan JY, et al. Altered polarization, morphology, and impaired innate immunity germane to resident peritoneal macrophages in mice with long-term type 2 diabetes. J Biomed Biotechnol 2012; 2012: 867023.
  4. Won JC, Kwon HS, Kim CH, Lee JH, Park TS, Ko KS, et al. Prevalence and clinical characteristics of diabetic peripheral neuropathy in hospital patients with Type 2 diabetes in Korea. Diabet Med 2012; 29(9): e290-e296.
  5. Wlodkowic D, Skommer J, McGuinness D, Hillier C, Darzynkiewicz Z. ER-Golgi network--a future target for anti-cancer therapy. Leuk Res 2009; 33(11): 1440-7.
  6. Kerner W, Bruckel J. Definition, classification and diagnosis of diabetes mellitus. Exp Clin Endocrinol Diabetes 2014; 122(7): 384-6.
  7. Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: Principles of pathogenesis and therapy. Lancet 2005; 365(9467): 1333-46.
  8. Szegezdi E, Logue SE, Gorman AM, Samali A. Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 2006; 7(9): 880-5.
  9. Oshitari T, Hata N, Yamamoto S. Endoplasmic reticulum stress and diabetic retinopathy. Vasc Health Risk Manag 2008; 4(1): 115-22.
  10. Bravo R, Parra V, Gatica D, Rodriguez AE, Torrealba N, Paredes F, et al. Endoplasmic reticulum and the unfolded protein response: Dynamics and metabolic integration. Int Rev Cell Mol Biol 2013; 301: 215-90.
  11. Kim Y, Park M, Boghossian S, York DA. Three weeks voluntary running wheel exercise increases endoplasmic reticulum stress in the brain of mice. Brain Res 2010; 1317: 13-23.
  12. Cao SS, Kaufman RJ. Targeting endoplasmic reticulum stress in metabolic disease. Expert Opin Ther Targets 2013; 17(4): 437-48.
  13. Morrow TJ. Animal models of painful diabetic neuropathy: The STZ rat model. Curr Protoc Neurosci 2004; 9: 9.18.
  14. Soya H, Nakamura T, Deocaris CC, Kimpara A, Iimura M, Fujikawa T, et al. BDNF induction with mild exercise in the rat hippocampus. Biochem Biophys Res Commun 2007; 358(4): 961-7.
  15. Singleton JR, Smith AG, Marcus RL. Exercise as therapy for diabetic and prediabetic neuropathy. Curr Diab Rep 2015; 15(12): 120.
  16. Wu J, Ruas JL, Estall JL, Rasbach KA, Choi JH, Ye L, et al. The unfolded protein response mediates adaptation to exercise in skeletal muscle through a PGC-1alpha/ATF6alpha complex. Cell Metab 2011; 13(2): 160-9.
  17. Pereira BC, da Rocha AL, Pinto AP, Pauli JR, de Souza CT, Cintra DE, et al. Excessive eccentric exercise-induced overtraining model leads to endoplasmic reticulum stress in mice skeletal muscles. Life Sci 2016; 145: 144-51.
  18. Dunys J, Duplan E, Checler F. The transcription factor X-box binding protein-1 in neurodegenerative diseases. Mol Neurodegener 2014; 9: 35.
  19. Wei M, Ong L, Smith MT, Ross FB, Schmid K, Hoey AJ, et al. The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes. Heart Lung Circ 2003; 12(1): 44-50.
  20. Chae CH, Jung SL, An SH, Jung CK, Nam SN, Kim HT. Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats. J Physiol Biochem 2011; 67(2): 235-41.
  21. Liu X, Zhang R, Huang L, Zheng Z, Vlassara H, Striker G, et al. Excessive oxidative stress contributes to increased acute ER stress kidney injury in aged mice. Oxid Med Cell Longev 2019; 2019: 2746521.
  22. Hamedifar M, Mirnasuri R, Rahmati M. The effects of six weeks endurance training on XBP-1 protein in the diabetic male wistar rats sciatica tissues. Iran J diabetes Obes 2018; 10(4): 187-93.
  23. Verdile G, Fuller SJ, Martins RN. The role of type 2 diabetes in neurodegeneration. Neurobiol Dis 2015; 84: 22-38.
  24. Zhang X, Xu L, He D, Ling S. Endoplasmic reticulum stress-mediated hippocampal neuron apoptosis involved in diabetic cognitive impairment. Biomed Res Int 2013; 2013: 924327.
  25. Hulmi JJ, Hentila J, DeRuisseau KC, Oliveira BM, Papaioannou KG, Autio R, et al. Effects of muscular dystrophy, exercise and blocking activin receptor IIB ligands on the unfolded protein response and oxidative stress. Free Radic Biol Med 2016; 99: 308-22.
  26. Hong J, Kim K, Kim JH, Park Y. The role of endoplasmic reticulum stress in cardiovascular disease and exercise. Int J Vasc Med 2017; 2017: 2049217.
  27. Park SM, Kang TI, So JS. Roles of XBP1s in transcriptional regulation of target genes. Biomedicines 2021; 9(7): 791.