The effect of six weeks of aerobic exercise on the expression of genes involved in aortic tissue pyroptosis of healthy and diabetic male mice

Subject Areas :

samira  hasanpoor solimani ¹ (PhD student of Exercise Physiology, Department of Physical Education &Sport Sciences, Islamic Azad University, Ayatollah Amoli Branch Amol, Iran.)
asieh  abbassi daloii ² (Associate Professor, Department of Physical Education &Sport Sciences , Ayatollah Amoli Branch, Islamic Azad University Amol, Iran)
Ahmad  Abdi ³ (Department of Exercise Physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran)
shirin  zilaei bouri ⁴ (Assistant Professor, Department of Physical Education &Sport Sciences, Izeh Branch, Islamis Azad University, Izeh. Masjed-Soleiman, Iran)

Received: 2021-12-11 Accepted : 2022-02-05 Published : 2022-02-20

Keywords: Regular Aerobic Exercise, NLRP3, : Diabetes, Pyroptosis,

Abstract :

Inroduction & Objective: In diabetes, inflammatory processes play a key role and affect all the complications of diabetes. Inflammation is associated with the caspase-1 process, which activates the anti-inflammatory cytokines IL-1β and IL-18, leading to the death of inflammatory proteins, which is one of the occurrences of pyroptosis. The aim of this study was to investigate the effect of six weeks of aerobic exercise on the expression of genes involved in aortic tissue apoptosis in healthy and diabetic mice. Materials and Methods: For this purpose, forty male rats (8 weeks old) were divided into 4 groups (10 in each group) after familiarization with exercise protocol: 1) control-healthy, 2) control-diabetes, 3) exercise-diabetes, and 4) exercise. -Healthy. Diabetes model was first induced, then run for 5 days on treadmill for 6 weeks. After 12 to 14 hours of fasting and 72 hours after the last training session, aortic tissue sampling was performed for IL-1β, IL-18, NLRP3 and Caspase-1 analysis by Real Time PCR technique. Data analysis was performed using one-way ANOVA, if significant difference was seen by Tukey post hoc test to determine the difference between groups (P <0.05). Results: Induction of diabetes led to a significant increase in IL-1β, IL-18, NLRP3 and Caspase-1 genes expression in rat aorta, which resulted in a significant decrease in aerobic exercise. Also, aerobic exercise in healthy mice also decreased the expression of IL-1β, IL-18, NLRP3 and Caspase-1 gene in aortic tissue. Conclusion: Aerobic exercise may be used as an effective non-pharmacological method to improve diabetes-induced inflammation and prevent vascular disorders.

References:

1.Abderrazak, T., Syrovets, D., Couchie, K., El Hadri, B., Friguet, T. (2015). NLRP3 inflammasome: from a danger signal sensor to a regulatory node ofoxidative stress and inflammatory diseases. Redox Biol, 4; 296–307.

2 Byun,.B.-J., Kim, Y. S., Lee, I.-S., Kim, J. S. (2017). Homonoia riparia and its major component, myricitrin, inhibit high glucose- induced apoptosis of human retinal pericytes. Integrative Medicine Research, 6(3); 300–309.

3.Brennan, MA., Cookson, BT. (2000). Salmonella induces macrophage death bycaspase-1-dependent necrosis. Mol Microbiol, 38(1); 31–40.

4.Carlsson, LM., Marklund, SL., Edlund, T. (1996). The rat extra cellular super oxide dismutase dimer is converted to a tetramer by the exchange of a singleamino acid. Proc Natl Acad Sci USA, 93; 5219–5222.

5.Chae, CH., Jung, SL., An, SH., Jung, CK., Nam, SN., Kim, HT. (2011). 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, 7; 235–241.

6.Chae, JJ., Cho, YH., Lee, GS., Cheng, J., Liu, PP., Feigenbaum, L. (2011). Gain-of-function Pyrin mutations induce NLRP3 protein-independent interleukin-1beta activation and severe autoinflammation in mice. Immunity, (5); 755–68.

7.Contreras, C., González-García, I., Martínez-Sánchez, N., Seoane-Collazo, P., Jacas, J., Morgan, D.A. (2014). Central ceramide-induced hypothalamic lipotoxicity and ER stress regulate energy balance. Cell Rep, 9; 366–377.

8.Fink, SL., Cookson, BT. (2006). Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell Microbiol, 8(11); 1812–25.

9. 9. Fyre, H., Baune, B.T. (2012). Neuroplastic changes in depression: a role for the immunesystem. Psycho Neuroendo Crinology, 37; 1397–1416.


10. 10. Ji, H., Miao, W., Ma, J., Xv, Z., Bo, H., Li, J. (2016). Acute exercise-induced mitochondrial stress triggers an inflammatory response in the myocardiumvia NLRP3 inflammasome activation with mitophagy, Oxid. Med. Cell. Longevity, 19; 87-149.

11.Jinhua, Gan., Liu, L., Fangyuan Xu. (2020). High glucose induces the loss of retinal pericytes partly via NLRP3-Caspase-1-GSDMD-mediated pyroptosis. Hindawi. BioMed Research International. Article ID 4510628, 12 pages.

12.Ken, Sh., Kazuhiko, I., Takuya, S. (2017). Regular voluntary exercise potentiates interleukin-1𝛽 and interleukin-18 secretion by increasing Caspase-1 expression in murine macrophages. Hindawi, Mediators of Inflammation. Article ID 9290416, 11 pages.

13.Khaleeli, E., Peters, S. R., Bobrowsky, K., Oudiz, R. J., Ko, J. Y., Budoff, M.J. (2001). Diabetes and the associated incidence of subclinical atherosclerosisand coronary artery disease: implications for management. Am. Heart J., 141; 637–644.

14.Malekshahi Nia, H., Dehkhoda, MR., Ahangarpour, A., Rajabi, H. (2018). The effect of 6 weeks aerobic training on insulin resistance, nitric oxide and some lipid profiles of type 2 diabetic male rats. Jundishapur Sci Med J , 17(4); 401-413. [Farsi]

15.Menu, P., Mayor, A., Zhou, R., Tardivel, A., Ichijo, H., Mori, K., Tschopp, J. (2012). ER stress activates the NLRP3 inflammasome via an UPR-independent pathway. Cell Death Dis., 3, e261.

16.Minami, A., Ishimura, N., Harada, N., Sakamoto, S., Niwa, Y., Nakaya, Y. (2002). Exercise training improves acetylcholine-induced endothelium-dependent hyper polarization in type 2 diabetic rats, Otsuka Long-Evans Tokushimafatty rats. Atherosclerosis, 162; 85–92.

17.Mishra, P.K., Adameová, A., Hill, J.A., Baines, C.P., Kang, P.M., Downey, J. (2019). Guidelines for evaluating myocardial cell death. Am. J. Physiol. Heart Circ. Physiol, 317; H891–H922.

18.Palsamy, P., Subra Mahian, S. (2008). Reaveratrol, a natural phytoalexin normalizes hyper glyciemia in strepozotocin nicotinamide  induced experimental diabetic rats. Biomedicin & Phalmacotherapy, 62; 598 – 605.

19.Panahzadeh, F., Mirnasuri, R., Rahmati, M. (2020). The effect of endurance training on the expression of PRDX6 and KAT2B genes in hippocampus of beta amyloid-induced rat model of alzheimer's disease: An Experimental Study. J Rafsanjan Univ Med Sci, 19(5); 485-98. [Farsi]

20.Paramel Varghese, G., Folkersen, L., Strawbridge, R. J., Halvorsen, B.,Yndestad, A., Ranheim, T. (2016). NLRP3 inflammasome expression and activation in human atherosclerosis. J. Am. Heart Assoc, 5; e003031.

21.Paterniti, I., Di Paola, R., Campolo, M., Siracusa, R., Cordaro, M., Bruschetta, G. (2015). Palmitoyl ethanolamide treatment reduces retinal inflammationin streptozotocin-induced diabetic rats. Eur. J. Pharmacol, 769; 313–323.

22. 22. Reaburn, P., Stanton, R. (2014). Exercise and the treatment of depression: a review ofthe exercise program variables, J. Sci. Med. Sport, 17; 177–182.

23.Rader, D. J. (2012). IL-1 and atherosclerosis: a murine twist to an evolving humanstory. J. Clin. Invest, 122; 27–30.

24.Rios, E.C.S., Szczesny, B., Soriano, F.G., Olah, G., Szabo, C. (2015). Hydrogen sulfide attenuates cytokine production through the modulation of chromatin remodeling. Int. J. Mol. Med, 35; 1741–1746.

25.Ruiz, S., Pergola, P. E., Zager, R. A., Vaziri, N. D. (2013). Targeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation inchronic kidney disease. Kidney Int, 83; 1029–1041.

26 Rubartelli, A,. Carta, S., Lavieri, R. (2013). Different members of the IL-1 family come out in different ways: DAMPs vs. cytokines?” Frontiers in Immunology, 4; article 123.

27.Sakamoto, S., Minami, K., Niwa, Y., Ohnaka, M., Shima, K. (1998). Effect of exercise training and food restrictionon endothelium-dependent relaxation in the Otsuka Long-Evans Tokushimafatty rat, a model of spontaneous NIDDM. Diabetes, 47; 82–86.

28.Sharma, A., Tate, M., Mathew, G.,Vince, JE., Ritchie, RH., de Haan, JB. (2018). Oxidative stress and NLRP3-inflammasome activity as significant drivers of diabetic cardiovascular complications: therapeutic implications. Front. Physiol, 9; 114.

29.Shi, X., Xie, W. L., Kong, W. W., Chen, D., (2015). Expression of the NLRP3 inflammasome in carotid atherosclerosis. j. stroke cerebrovasc. Dis.,24; 2455–2466.

30.Shirwaikar, A., Rajendran, K., Punitha, ISR. (2005). Antidiabetic activity of alcoholic stem extract of coscinium fenestratum in streptozotocin-nicotinamide induced type 2 diabetic rats. Journal of Ethnopharmacology, 97; 369–374.

31.Sigal, RJ., Kenny, GP., Wasserman, DH., Castaneda-Sceppa, C., White, RD. (2006). Physical activity/exercise and type 2 diabetes: a consensus statement fromthe American Diabetes Association. Diabetes Care, 29; 1433–1438.

32.Skerrett, PJ., Horton, E. (2002). Exercise and diabetes prevention: reduction in risk of coronary heart disease. In: Handbook of Exercise in Diabetes, edited by Ruderman NB, Devlin JT, Schneider SH, and Kriska A. Alexandria: American Diabetes Association, 155–182.

33.Strowig, T.; Henao-Mejia, J.; Elinav, E.; Flavell, R. (2012). Inflammasomes in health and disease. Nature, 481, 278.

34.Sumit, Kar., Hamid, R. (2019). Exercise training promotes cardiac hydrogen sulfide biosynthesis and mitigates pyroptosis to prevent high-fat diet-induced diabetic cardiomyopathy. Antioxidants, 8; 638.

35.Wilding, J. P. H. (2018). Medication use for the treatment of diabetes in obese individuals. Diabetologia, 61; 265–272.

36.Yang, Y. Giang, J. Ghang, P. Fan, J. (2015). Programmed cell death and its role in inflammation. Military Medical Research, 2;12.

37.Yujun, W., Yongjun, Xu. (2016). Exercise amelioration of depression-like behavior in OVX mice is associated with suppression of NLRP3 inflammasome activation in hippocampus. Behavioural Brain Research, 307; 18–24.

38. Zapasi, Z.F., Catlin, P.A., Beck, J. (2001). The role of endogenousopioids in moderate exercise training-induced enhancement of the secondary antibody response in mice, Phys. Ther, 81;1801–1809.