Research Article
Volume 9 Issue 4 - 2022
β2-Adrenoceptor and Expression of MuRF1 and Atrogin-1 Under Stress
Ricardo Moura, Marco Antonio Cordeiro, Alessandra Medeiros, Daniela Ortolani, Daniel Araki Ribeiro, Ana Elisa Teófilo Saturi de Carvalho and Regina Celia Spadari*

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

*Corresponding Author: Regina Celia Spadari, Department of Biosciences, Federal University of São Paulo (UNIFESP), Santos, SP, Brazil.
Received: June 15, 2022; Published: June 18, 2022


Background: Stress is an important risk factor for cardiovascular diseases. During the stress reaction, catecholamines released by the sympathetic nervous system and the adrenal medulla couple to β-adrenoceptors (β-AR) in almost every organ. In the heart, β1- (β1-AR) and β2-adrenoceptors (β2-AR) are expressed in an 80:20 ratio, and control heart functioning (via the Gs protein-adenylyl-cyclase signaling pathway) as well as cardiomyocytes life cycle (via the Gi-PI3K-Akt pathway). Changes in β1-AR/β2-AR ratio were associated with poor cardiac performance and can be triggered by stress. The putative consequences of those stress-induced changes on cardiac atrophy/pathological hypertrophy were not explored yet. This work aims to investigate the role played by β2-AR in the expression of components of the PI3K-Akt signaling pathway in the heart of rats submitted to foot shock stress.

Material and Method: Adult male rats were distributed in four groups: control, stress, ICI118,551 treated, and stress + ICI118,551 treated. Rats were submitted to one daily session of foot-shock stress (30 min duration, 1 mA, 1 s duration at random intervals between 5 and 25 s) during 3 days. ICI was administered i.p., 2 days before and during the stress period. The expression of proteins was analyzed by Western blot in the heart of rats sacrificed immediately after the last stress session.

Results: Foot-shock stress induced a reduction in the expression of MuRF1 whereas atrogin-1 and C2 proteasome expressions were unaltered. In the heart of stressed rats treated with the β2-AR antagonist (ICI118,551) there was down regulation of pAkt and atrogin-1 whereas MuRF1 and C2 proteasome were up regulated.

Conclusion: The β2-AR plays a role in the control of the signaling pathways leading to the expression of MuRF1, atrogin-1 and C2 proteasome under stress, probably protecting the heart against atrophy and pathological hypertrophy.


Keywords: β2 adrenoceptor; Atrogin-1; MuRF1; Cardiac Remodeling; Stress


  1. Levy D., et al. “Prognostic implications of echocardiographically determined left ventricular mass in the Framingham heart study”. New England Journal of Medicine 322 (1990): 1561-1566.
  2. Shimizu I and Minamino T. “Physiological and pathological cardiac hypertrophy”. Journal of Molecular and Cellular Cardiology 97 (2016): 245-262.
  3. Skurk C., et al. “The FOXO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling”. Journal of Biological Chemistry 280 (2005): 20814-20823.
  4. Paradis S and Ruvkun G. “Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor”. Genes Development 12 (1998): 2488-2498.
  5. Sandri M., et al. “Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy”. Cell 117 (2004): 399-412.
  6. Silveira WA., et al. “Activating cAMP/PKA signaling in skeletal muscle suppresses the ubiquitin-proteasome-dependent proteolysis: implications for sympathetic regulation”. Journal of Applied Physiology 117 (2014): 11-19.
  7. Gomes MD., et al. “Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy”. Proceedings of the National Academy of Science USA 98 (2001): 14440-14445.
  8. Pagan J., et al. “Role of the ubiquitin proteasome system in the heart”. Circulation Research 112 (2013): 1046-1058.
  9. Arya R., et al. “Muscle ring finger protein-1 inhibits PKC {epsilon} activation and prevents cardiomyocyte hypertrophy”. Journal of Cell Biology 167 (2004): 1147-1159.
  10. Li HH., et al. “Atrogin-1/muscle atrophy F-box inhibits calcineurin-dependent cardiac hypertrophy by participating in an SCF ubiquitin ligase complex”. Journal of Clinical Investigation 114 (2004): 1058-1071.
  11. Rodríguez JE., et al. “The ubiquitin ligase MuRF1 regulates PPARα activity in the heart by enhancing nuclear export via monoubiquitination”. Molecular Cell Endocrinology 413 (2015): 36-48.
  12. Mearini G., et al. “Atrogin-1 and MuRF1 regulate cardiac MyBP-C levels via different mechanisms”. Cardiovascular Research 85 (2010): 357-366.
  13. Manning BD and Toker A. “AKT/PKB signaling: Navigating the network”. Cell 169 (2017): 381-405.
  14. Xiao RP., et al. “Functional coupling of the beta 2-adrenoceptor to a pertussis toxin-sensitive G protein in cardiac myocytes”. Molecular Pharmacology 47 (1995): 322-329.
  15. Xiao RP., et al. “Coupling of beta2-adrenoceptor to Gi proteins and its physiological relevance in murine cardiac myocytes”. Circulation Research 84 (1999a): 43-52.
  16. Xiao RP., et al. “Recent advances in cardiac beta (2)-adrenergic signal transduction”. Circulation Research 85 (1999b): 1092-1100.
  17. Zhang W., et al. “Adrenergic Receptor-PI3K Signaling Crosstalk in Mouse Heart: Elucidation of Immediate Downstream Signaling Cascades”. Plos One 10(2011): e26581.
  18. Juberg EN., et al. “β1-and β2-adrenoceptor binding and functional response in right and left atria of rat heart”. Naunyn-Schmiedeberg Archieves of Pharmacology 3 (1985): 193-202.
  19. Kaumann AJ and Molenaar P. “Modulation of human cardiac function through 4 β-adrenoceptor populations”. Naunyn-Schmiedeberg Archieves of Pharmacology 6 (1997): 667-681.
  20. Woo AYH and Xiao RP. “β-Adrenergic receptor subtype signaling in heart: from bench to bedside”. Acta Pharmacologica Sineca 3(2012): 335-341.
  21. Rehsia NS and Dhalla NS. “Mechanisms of the beneficial effects of beta-adrenoceptor antagonists in congestive heart failure”. Experimental and Clinical Cardiology 4 (2010): e86-95.
  22. Lymperopoulos A., et al. “Adrenergic nervous system in heart failure: pathophysiology and therapy”. Circulation Research 6 (2013): 739-753.
  23. Ferrara N., et al. “Beta-adrenergic receptor responsiveness in aging heart and clinical implications”. Frontiers in Physiology 4 (2014): 1-10.
  24. Erdogan BR., et al. “Expression and Signaling of vβ-Adrenoceptor Subtypes in the Diabetic Heart”. Cells12 (2020): 2548.
  25. Santos IN and Spadari-Bratfisch RC. “Stress and cardiac beta adrenoceptors”. Stress 9 (2006): 69-84.
  26. Spadari RC., et al. “Role of beta-adrenergic receptors and sirtuin signaling in the heart during aging, heart failure, and adaptation to stress”. Cellular and Molecular Neurobiology 1 (2018): 109-120.
  27. Bassani RA and De Moraes S. “Effects of footshock stress on the sensitivity of the isolated rat pacemaker to catecholamines”. Brazilian Journal of Medical and Biological Research4 (1987): 467-470.
  28. Moura AL., et al. “Functional β2-adrenoceptors in rat left atria: effect of foot-shock stress”. Canadian Journal of Physiology and Pharmacology 9 (2017): 999-1038.
  29. De Carvalho AETS., et al. “Stress-induced differential gene expression in cardiac tissue”. Scientific Reports 11 (2021): 9129.
  30. Cordeiro MA., et al. “Persistent effects of subchronic stress on components of ubiquitin-proteasome system in the heart”. Journal of Clinical and Experimental Cardiology 11 (2020): 676.
  31. Bassani RA and De Moraes S. “Functional beta 2-adrenoceptors in right atria isolated from footshock-stressed rats”. Brazilian Journal of Medical and Biological Research 3 (1988): 557-559.
  32. Verago JL., et al. “Metabolic markers following beta-adrenoceptor agonist infusion in footshock-stressed rats”. Brazilian Journal of Medical and Biological Research9 (2001): 1197-1207.
  33. Ortolani D., et al. “Effects of comfort food on food intake, anxiety-like behavior and the stress response in rats”. Physiology and Behavior 103 (2011): 487-492.
  34. Ruffolo RRJ. “Adrenoceptors: Structure, Function and Pharmacology”. Hardwood Academic Luxembourg (1997): 279.
  35. Willis MS., et al. “Muscle ring finger 1 mediates cardiac atrophy in vivo”. American Journal of Physiology: Heart Circulation Physiology 296 (2009a): H997-H1006.
  36. Barac YD., et al. “The ubiquitin-proteasome system: a potential therapeutic target for heart failure”. Journal of Heart and Lung Transplant 36 (2017): 708-714.
  37. Knaapen MW., et al. “Apoptotic versus autophagic cell death in heart failure”. Cardiovascular Research 51 (2001): 304-312.
  38. Adams V., et al. “Myocardial expression of Murf-1 and MAFbx after induction of chronic heart failure: Effect on myocardial contractility”. Circulation Research 73 (2007): 120-129.
  39. Kedar V., et al. “Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I”. Procedings of the National Academy of Science USA 10 (2004): 18135-18140.
  40. Witt SH., et al. “Murf-1 and Murf-2 target a specific subset of myofibrillar proteins redundantly: towards understanding Murf-dependent ubiquitination”. Journal of Molecular Biology 350 (2005): 713-722.
  41. Van der Velden J., et al. “Alteration in myofilament function contributes to left ventricular dysfunction in pigs early after myocardial infarction”. Circulation Research 95 (2004): e85-95.
  42. Anker S., et al. “Tumor necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting”. Journal of American College of Cardiology 30 (1997): 997-1001.
  43. Abid M. R., et al. “Vascular endothelial growth factor activates PI3K/Akt/forkhead signaling in endothelial cells”. Arteriosclerosis, Thrombosis, and Vascular Biology 24 (2004): 294-300.
  44. Adjelkovic M., et al. “Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors”. Proceedings of the National Academy of Sciences USA 93 (1996): 5699-56704.
  45. Guo H., et al. “Coordinate phosphorylation of multiple residues on single AKT1 and AKT2 molecules”. Oncogene 33 (2014): 3463-3472.
  46. Weekes J., et al. “Hyperubiquitination of proteins in dilated cardiomyopathy”. Proteomics (2003) 2: 208-216.
  47. Galasso G., et al. “Myocardial expression of FOXO3a-Atrogin-1 pathway in human heart failure”. European Journal of Heart Failure 12 (2010): 1290-1296.
Citation: Regina Celia Spadari., et al. “β2-Adrenoceptor and Expression of MuRF1 and Atrogin-1 Under Stress”. EC Gynaecology 9.4 (2022): 20-30.

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