Ana Elisa T.S. de Carvalho*, Marco A. Cordeiro, Luana S. Rodrigues, Daniela Ortolani, Regina C. Spadari*

Department of Biosciences, Federal University of São Paulo (UNIFESP), Santos, SP, Brazil

Stress has emerged as a factor associated with cardiovascular disease. Catecholamines released during the stress reaction by the sympathetic nerves and the adrenal medulla couple to β1-and β2-adrenoceptors in the cardiomyocytes membrane enhancing heart function in order to attend the organism demand. This might produce excessive reactive oxygen species what may culminate with oxidative stress and progression of several cardiac diseases. Sirtuins have been described as cardioprotective factors and important regulators of the cellular stress response in the heart. The aim of this work is to investigate the putative participation of oxidative stress and sirtuins in the heart of rats submitted to foot shock stress, an experimental model where there is up regulation of β2-adrenoceptors and downregulation of β1-adrenoceptors. The data have shown that in the myocardium of rats submitted to foot shock stress the H2O2 concentration, catalase and superoxide dismutase activity, NAD+/NADH ratio, as well as the protein expression of sirtuins 1 and 3 were not altered. Pharmacological blockade of the β2-adrenoceptors by ICI118,551, did not modify this scenario. It is concluded that foot shock stress does not cause disruptions in oxidative stress or redox state processes in the myocardium, and consequently, sirtuins are not recruited to stress response.

Keywords: oxidative stress, sirtuins, foot shock stress, β2-adrenoceptor

Free Full-text PDF

How to cite this article:
Ana Elisa T.S. de Carvalho, Marco A. Cordeiro, Luana S. Rodrigues, Daniela Ortolani, Regina C. Spadari. Absence of oxidative stress and sirtuins recruitment on cardiac tissue post stress.American Journal of Cardiology Research and Reviews, 2022, 5:19. DOI:10.28933/ajcrar-2021-10-2205


1. Santos IN, Spadari-Bratfisch RC. Stress and cardiac beta adrenoceptors. Stress, 2006, 9 (2): 69-84. DOI: 10.1080/10253890600771858.
2. Rehsia NS, Dhalla NS. Mechanisms of the beneficial effects of beta-adrenoceptor antagonists in congestive heart failure. Experimental and Clinical Cardiology, 2010, 15 (4): e86-e95. PMC3016066.
3. Lymperopoulos A, Rengo G, Koch WJ. Adrenergic nervous system in heart failure: pathophysiology and therapy. Circulation Research, 2013, 6: 739-753. DOI: 10.1161/CIRCRESAHA.113.300308.
4. Moura AL, Hyslop S, Grassi-Kassisse DM, Spadari RC. Functional β2-adrenoceptors in rat left atria: effect of foot-shock stress. Canadian Journal of Physiology and Pharmacology, 2017, 9: 999-1038. DOI: dx.doi.org/10.1139/cjpp-2016-0622.
5. Spadari RC, Cavadas C, De Carvalho AETS, Ortolani D, de Moura AL, Vassalo PF. Role of beta-adrenergic receptors and sirtuin signaling in the heart during aging, heart failure, and adaptation to stress. Cellular and Molecular Neurobiology, 2018, 1: 109-120. DOI: 10.1007/s10571-017-0557-2.
6. Spadari RC, Bassani RA, De Moraes S. Supersensitivity to isoprenaline and epinephrine in right atria isolated from rats submitted to a single swimming session. General Pharmacology: The Vascular System, 1988, 1: 129-35. DOI: 10.1016/0306-3623(88)90018-3.
7. Santos CXC, Anilkumar N, Zhang M, Brewer AC, Shah AM. Redox signaling in cardiac myocytes. Free Radical Biology & Medicine, 2011, 50: 777–793. DOI:10.1016/j.freeradbiomed.2011.01.003.
8. Hill MF & Singal PK. Antioxidant and oxidative Stress changes during heart failure subsequent to myocardial infarction in rats. American Journal of Pathology, 1996, 148 (1): 291–300. PMC1861605.
9. van der Pol A, van Gilst HW, Voors AA, van der Meer P. Treating oxidative stress in heart failure: past, present and future. European Journal of Heart Failure, 2019, 21: 425– 435. DOI:10.1002/ejhf.1320.
10. Corbi G, Conti V, Russomanno G, Longobardi G, Furgi G, Filippelli A, Ferrara N. Adrenergic signaling and oxidative stress: a role for sirtuins? Frontiers in Physiology, 2013, 8 (4): 324. DOI: 10.3389/fphys.2013.00324.
11. Tanno M, Kuno A, Horio Y, Miura T. Emerging beneficial roles of sirtuins in heart failure. Basic Research in Cardiology, 2012, 107(4): 273. DOI: 10.1007/s00395-012-0273-5.
12. Frescas D, Valenti L, Accili D. Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes. The Journal of Biological Chemistry, 2005, 280 (21): 20589–20595. DOI: 10.1074/jbc.M412357200.
13. Sundaresan NR, Samant SA, Pillai VB, Rajamohan SB, Gupta MP. SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70. Molecular and Cellular Biology, 2008, 28 (20): 6384–6401. DOI: 10.1128/MCB.00426-08.
14. Sciarretta S, Hariharan N, Monden Y, Zablocki D, Sadoshima J. Is autophagy in response to ischemia and reperfusion protective or detrimental for the heart? Pediatric Cardiology, 2011, 32 (3): 275–81. DOI: 10.1007/s00246-010-9855-x.
15. Sundaresan NR, Gupta M, Kim G, Rajamohan SB, Isbatan A, Gupta MP. Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. The Journal of Clinical Investigation, 2009, 119: 2758– 2771. DOI: 10.1172/JCI39162.
16. Pillai VB, Sundaresan NR, Jeevanandam V, Gupta MP. Mitochondrial SIRT3 and heart disease. Cardiovascular Research, 2010, 88 (2): 250–256. DOI: 10.1093/cvr/cvq250.
17. Grillon JM, Johnson KR, Kotlo K, Danziger RS. Non-histone lysine acetylated proteins in heart failure. Biochimica et Biophysica Acta, 2012, 1822(4): 607-14. DOI: 10.1016/j.bbadis.2011.11.016.
18. Koentges C, Bode C, Bugger H. SIRT3 in Cardiac Physiology and Disease. Frontiers in Cardiovascular Medicine, 2016; 3: 38. DOI: 10.3389/fcvm.2016.00038.
19. Alcendor RR, Kirshenbaum LA, Imai S, Vatner SF, Sadoshima J. Silent information regulator 2alpha, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes. Circulation Research, 2004, 95 (10): 971–980. DOI: 10.1161/01.RES.0000147557.75257.
20. Pillai JB, Isbatan A, Imai S, Gupta MP. Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity. The Journal of Biological Chemistry, 2005, 280 (52): 43121–30. DOI: 10.1074/jbc.M506162200.
21. Alcendor RR, Gao S, Zhai P, Zablocki D, Holle E, Yu X, Tian B, Wagner T, Vatner SF, Sadoshima J. Sirt1 regulates aging and resistance to oxidative stress in the heart. Circulation Research, 2007,100:1512–1521. DOI: 10.1161/01.RES.0000267723.65696.4a.
22. Hsu CP, Zhai P, Yamamoto T, Maejima Y, Matsushima S, Hariharan N, Shao D, Takagi H, Oka S, Sadoshima J. Silent information regulator 1 protects the heart from ischemia/reperfusion. Circulation, 2010, 122:2170–2182. DOI: 10.1161/CIRCULATIONAHA.110.958033.
23. Matsushima S & Sadoshima J. The role of sirtuins in cardiac disease. American Journal of Physiology: Heart and Circulatory Physiology 309 (9): H1375–H1389, 2015. DOI:10.1152/ajpheart.00053.2015.
24. Ortolani D, Oyama LM, Ferrari EM, Melo LL, Spadari-Bratfisch RC. Effects of comfort food on food intake, anxiety-like behavior and the stress response in rats. Physiology and Behaviour, 2011, 103(5): 487-492. DOI: 10.1016/j.physbeh.2011.03.028.
25. Cordeiro MA, Rodrigues LS, Ortolani D, de Carvalho AET, Spadari RC. Persistent effects of subchronic stress on components of ubiquitin-proteasome system in the heart. Journal of Clinical and Experimental Cardiology, 2020, 11: 676. DOI: 35248/2155-9880.20.
26. Elkhwanky MS & Hakkola J. Extranuclear sirtuins and metabolic stress. Antioxidants & Redox Signaling, 2018, 28 (8): 662-676. DOI: 10.1089/ars.2017.7270.
27. de Carvalho AETS, Cordeiro MA, Rodrigues LS, Ortolani D, Spadari RC. Stress-induced differential gene expression in cardiac tissue. Scientific Reports, 2021, 11: 9129. DOI: 10.1038/s41598-021-88267-8.
28. Takimoto E & Kass DA. Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension, 2007, 49 (2): 241–248. DOI: 10.1161/01.HYP.0000254415.31362.a7.
29. Wang L, Quan N, Sun W, Chen X, Cates C, Rousselle T, Zhou X, Zhao X and Li J. Cardiomyocyte-specific deletion of Sirt1 gene sensitizes myocardium to ischaemia and reperfusion injury. Cardiovascular Research, 2018, 114 (6): 805–821. DOI: 10.1093/cvr/cvy033.
30. Luo G, Jian Z, Zhu Y, Zhu Y, Chen B, Ma R, Tang F and Xiao Y. Sirt1 promotes autophagy and inhibits apoptosis to protect cardiomyocytes from hypoxic stress. International Journal of Molecular Medicine, 2019, 43 (5): 2033-2043. DOI: 10.3892/ijmm.2019.4125.
31. Huang H & Tindall DJ. Dynamic FoxO transcription factors. Journal of Cell Science, 2007, 120: 2479–2487. DOI: 10.1242/jcs.001222.
32. Gomes AP, Price NL, Ling AJY, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, De Cabo R, Rolo AP, Turner N, Bell EL, and Sinclair DA. Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell, 2013, 155 (7): 1624–1638. DOI: 10.1016/j.cell.2013.11.037.
33. Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nature Reviews Molecular Cellular Biology, 2012, 13: 225–38. DOI: 10.1038/nrm3293.

Terms of Use/Privacy Policy/ Disclaimer/ Other Policies:
You agree that by using our site, you have read, understood, and agreed to be bound by all of our terms of use/privacy policy/ disclaimer/ other policies (click here for details)

CC BY 4.0
This work and its PDF file(s) are licensed under a Creative Commons Attribution 4.0 International License.