title: Molecular changes induced by repeated restraint stress in the heart: the effect of oxytocin receptor antagonist atosiban.
abstract: Even though stress belongs to the most common lifestyle risk factors of cardiovascular diseases, there are only limited data on direct influence of stressors on the heart. The aim of the present study was to explore selected protein signaling pathways in response to repeated immobilization stress in the heart tissue. Effects of simultaneous treatment with atosiban, an oxytocin receptor antagonist, on stress-induced changes in the heart were also investigated. Male Wistar rats were exposed to repeated immobilization (2 h daily, lasting 2 weeks). The results showed increased phosphorylation of Akt kinase, enhanced levels of Bcl-2, and decreased levels of cleaved caspase-3 in the left ventricle in response to chronic stress independently of the treatment. Exposure to restraint led to the rise of HSP-90 and p53 in vehicle-treated rats only. Stress failed to modify MMP-2 activity and ultrastructure of the heart tissue. Treatment with the oxytocin/vasopressin receptor antagonist atosiban reversed stress-induced rise in HSP-90 and p53 proteins. In conclusion, our data demonstrate that repeated restraint stress induces Akt kinase activation and this is associated with elevation of anti-apoptotic proteins (Bcl-2) and down-regulation of pro-apoptotic proteins (cleaved caspase-3). These findings suggest that activation of pro-survival anti-apoptotic Akt kinase pathway plays an important role in molecular mechanisms underlying responses and adaptation of the rat heart to repeated stress exposure. The results further indicate a regulatory role of oxytocin/vasopressin in the control of stress-induced activation in HSP-90 and related proteins.
authors: a Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.|d Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Slovak Republic.
authors: Monika
authors: M
authors: Bartekova
authors: a Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors: Miroslav
authors: M
authors: Barancik
authors: b Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors: Michal
authors: M
authors: Pokusa
authors: b Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic.|e Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Slovak Republic.
authors: Barbora
authors: B
authors: Prokopova
authors: a Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.|d Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Slovak Republic.
authors: Jana
authors: J
authors: Radosinska
authors: c Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors: Andrej
authors: A
authors: Rusnak
authors: c Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovak Republic.|f Institute of Biochemistry, Nutrition and Health Protection, Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, Slovak Republic.
authors: Albert
authors: A
authors: Breier
authors: b Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors: Daniela
authors: D
authors: Jezova
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors*; D012149:Restraint, Physical; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018841:HSP90 Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018045:Receptors, Oxytocin; C588222:oxytocin receptor, rat; C047046:atosiban; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D020778:Matrix Metalloproteinase 2; D014668:Vasotocin
keywords: atosiban; cœur; heart; protein signaling; restraint stress; signalisation protéique; stress de contention