Auswahl der wissenschaftlichen Literatur zum Thema „Adrenergní a tyroidní signalizace“

Despite advances in research and therapy, cardiovascular diseases are still the leading cause of death worldwide. A closer understanding of the endogenous protective mechanism may improve pharmacological interventions for the treatment of heart diseases. Cold acclimation or hardening has strong potential for reducing cardiovascular risk and the literature shows that it stimulates the β-adrenergic and thyroid systems in tissues. At the same time, the adrenergic system in the heart is one of the main regulators of cardiac activity. However, these signaling pathways have surprisingly not been studied at the protein level in the heart yet, and no studies can be found on the subject matter in current literature. Our results show a reduced infarct size induced by ischemic injury in cold-acclimated rats (CA) at 8 ř C for 5 weeks and then returning to normothermic conditions for 2 weeks (CAR). The aim of this dissertation is to determine, the degree of involvement of the adrenergic system in the myocardium during acclimation after 3 days, 10 days, 5 weeks of CA and subsequent CAR at the level of all three β-adrenergic receptor isoforms (β-ARs) and their signaling pathways. The results show unchanged signaling of β1-AR-Gs-adenylyl cyclase-protein kinase A in the cardioprotective regimes CA and CAR, whose...

Cardiovascular diseases are currently one of the most common causes of morbidity and mortality in the Western world. Adaptation to chronic hypoxia can contribute to the improvement of ischemic tolerance of myocardium but exact molecular mechanisms leading to the development of a cardioprotective phenotype are still unclear. There are some indications that point to the possible role of β-adrenergic signaling in these processes. In the first part of the thesis, we examined the effect of protective continuous (CNH; 24 h/day) and nonprotective intermittent (INH; 23 h/day hypoxia, 1 h/day reoxygenation) normobaric hypoxia on β-adrenergic signaling in the right (RV) and left ventricles (LV) of Wistar rats. Both hypoxic models led to decrease in the number of β1-adrenergic receptors (β1-ARs) in the RV. There were no significant changes in β-ARs in LV preparations. Although adenylyl cyclase (AC) activity stimulated through Gs proteins was decreased in the RV and increased in the LV after adaptation to CNH and INH, there were no significant changes in the expression of dominant AC 5/6 isoforms. Expression of Gs proteins was decreased in RV in both hypoxic models. These results suggest that chronic normobaric hypoxia may have a strong effect on myocardial β-adrenergic signaling without differences between...

2. Abstract The aim of this dissertation was to evaluate the effect of low doses (0,1 mg/kg, 1 mg/kg, 1 mg/kg per day for 28 days + 7 days of abstinence) and high doses (10 mg/kg per day for 10 days) of morphine on transmembrane signaling mediated by G-protein coupled receptors (GPCRs) in the rat myocardium. Opioid receptors (OR) and mainly β-adrenergic receptors (β-AR) belong to the most important receptors of this receptor family. δ-OR and κ-OR are the most numerous OR in the myocardium. Results of the present work indicated that there are no significant changes in the expression of these two receptor subtypes after any studied doses of morphine. There are three subtypes of β-AR (β1-AR, β2-AR and β3-AR) represent in the myocardial tissue. Here we studied the expression of β1-AR and β2-AR, because these two major subtypes of β-AR regulate through their signaling pathways functioning of the cardiovascular system. Our immunoblot analysis did not reveal any changes in the expression of β1-AR, but the expression of β2-AR was significantly decreased after treatment with morphine at the dose of 10 mg/kg for the 10 days. More sensitive saturation binding experiments with the nonselective β-antagonist [3 H]CGP 12177 indicated a significant increase in specific binding after treatment with morphine (1 mg/kg/day for...

Endogenous cardiac protection against acute ischemia/reperfusion injury can by increased by cardiac adaptation to various forms of chronic hypoxia. Chronic hypoxia induces a large variety of adaptive changes in the myocardium that could be considered as protective, but the exact mechanism of increased ischemic tolerance is unknown. Different studies suggest that catecholamine release and their effect on -adrenergic signaling after adaptation to chronic hypoxia contributes to cardioprotection. In this study we focused on characterization of -adrenergic receptors ( -ARs) in the myocardium of rats after adaptation to three different hypoxic conditions: 1. intermittent normobaric hypoxia - INH/R (23 h hypoxia, 1 h reoxygenation), 2. intermittent normobaric hypoxia - INH (8 h hypoxia, 16 h normoxia), 3. continuous normobaric hypoxia - CNH (24 h hypoxia). We compared how each hypoxic model affects the total number of -adrenergic receptors and proportion of individual subtypes ( 1-and 2-ARs) in the left and right ventricles compared control normoxic rats. The INH model had apparently no effect on -ARs in either ventricles. On the other hand, adaptation to INH/R and CNH was accompanied by a significant decrease (by about 25%) in the total number of -adrenergic receptors in the right ventricles. Our present...

β-Adrenergic signalization plays an important role in heart, regulating cardiac frequency and contractility. It is also involved in development of hypertension and heart hypertrophy. Spontaneous hypertensive rat strain is a common model for human essential hypertension, although the origin of blood pressure abnormalities in SHR remains unknown. Dysfunction in the regulation of fatty acid translocase Cd36 was suggested as a link to development of hypertension in SHR. Transgenic strain SHR-Tg19 (also known as SHR-Cd36) was obtained, harboring a wild type of FAT/Cd36. This thesis aimed to investigate key elements of β-adrenergic signaling in the heart of SHR-Tg19 compared to their SHR controls. Expression and distribution of β1- and β2-ARs were measured using radioligand binding and Western blot analysis along with expression of selected G proteins and expression and activity of adenylyl cyclase. Our experiments showed that there were no significant changes in the Gsα and Giα subunits expressions, along with the amount of β1-AR in both left and right ventricles, according to the Western immunoblotting, but radioligand binding showed an increase in the quantity of β-ARs, particularly β2 subtype. Alongside, an increased expression of β2- ARs was observed in the right ventricle. Different...

and keywords The aim of this work was to evaluate the effect on rat myocardial β-adrenergic system of short-term (10 hours and 3 days) and long-term (5 weeks) cold exposure of rats with possible subsequent two-week recovery at normal temperature. The subtypes of β-adrenergic receptors (β-AR), their cognate G-proteins and adenylate cyclase have been characterized. β-AR are important components of cardiac regulatory mechanisms. They are involved in stimulating G-protein (Gs) and adenylate cyclase to increase cardiac contractility and frequency during stressful situations, including cold exposure. Heart tissue contains all three β-AR subtypes (β1-AR, β2-AR, β3-AR). While β1-AR couples with only Gs, β2-AR and β3-AR interact with the inhibitory G-protein (Gi). Electrophoresis and Western blotting showed a significant increase in β1-AR after a three-day exposure to cold. There was also a significant increase in β3-AR concentrations after a five-week cold exposure and this increase lasted for two weeks. There were no significant changes in the amnounts of β-AR cognate G-proteins (Gαs, Gβ, Gαi1/2 a Gαi3). In contrast, expression of adenylyl cyclase isoform V and VI significantly decreased during short-term exposure to cold. Using the saturation experiment with the β-antagonist [3H]CGP 12177, β-AR were...

Acute cold exposure is a significant stressor activating heat production by shivering after the prolonged exposure cellular oxidative stress increases. Chronic exposure to cold lasting at least 2 weeks leads to the development of cold acclimatization. The main thermogenic role is taken over by non-shivering thermogenesis taking place in brown adipose tissue, which significantly increases its weight due to cold. Cardiac hypertrophy, hypertension and impaired renal function are frequently observed pathologies of acclimatization at 4-5 řC. Our laboratory recently introduced a model of mild chronic cold acclimatization at 8 řC, during which no damage to the heart or kidneys occurs and has proven cardioprotective effect on reducing infarct size. Hence, the influence of this cold acclimatization model on the other cellular and molecular processes needs to be investigated. The cardioprotective effect of cold acclimatization includes changes in β-AR signaling, activation of anti-apoptotic pathways or augmentation of the antioxidant system. The aim of this thesis was to investigate the effect of cold acclimation and subsequent reacclimation on proteins regulating Ca2+ levels in the rat heart (SERCA2 and phospholamban) and on the stimulation of regulatory proteins β-arrestin 1/2 and protein kinase PDPK1. The...

Acute cold exposure increases the risk of sudden cardiac events, similarly exposure to constant light negatively affects the cardiovascular system. However, the individual effects of these factors and the effect of their combination on cardiomyocytes are not yet known. The thesis deals with the influence of a 3 day cold exposure and constant light on the expression of β-adrenergic receptors and associated G-proteins in association with apoptotic signals in the left ventricle of the Wistar rat heart. In this work apoptotic proteins BAX, BCL2, caspase 8 and important components of β-adrenergic signalization - β1, β2, G-proteins, Gas, Gi1/2 and Gi3 were determined. The relative expression of the proteins was analyzed by Western blotting. The results confirm the detrimental effect of cold and light exposure. However, the synergistic effect of these two stressors shows surprising results.