Molecular changes induced by repeated restraint stress in the heart: the effect of oxytocin receptor antagonist atosiban
| Autor: | Andrej Rusnak, Michal Pokusa, Miroslav Barancik, Monika Bartekova, Barbora Prokopova, Albert Breier, Jana Radosinska, Daniela Jezova |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Restraint Physical medicine.medical_specialty Vasopressin Physiology Vasotocin Biology chemistry.chemical_compound Stress Physiological Physiology (medical) Internal medicine medicine Animals Chronic stress HSP90 Heat-Shock Proteins Vasopressin receptor Pharmacology Caspase 3 Myocardium Antagonist Atosiban Heart General Medicine Oxytocin receptor Rats Endocrinology chemistry Oxytocin Proto-Oncogene Proteins c-bcl-2 Receptors Oxytocin Matrix Metalloproteinase 2 Proto-Oncogene Proteins c-akt medicine.drug Signal Transduction |
| Zdroj: | Canadian journal of physiology and pharmacology. 93(9) |
| ISSN: | 1205-7541 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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