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Studies of cell signaling triggered by the TRH receptor
Trubačová, Radka
Activation of thyrotropin-releasing hormone receptor (TRH-R) signaling has an irreplaceable role in a number of cellular processes. Thyroliberin (TRH) plays an important role in the regulation of secretion of other hormones and there are also mentions of its possible antiapoptotic and neuroprotective effects. On the other hand, TRH is quickly degraded and also its other properties, such as cardiac and endocrine side effects and low lipophilicity, disadvantage the therapeutic applications of this hormone compared to its various analogues. Due to their effects on the central nervous systém, TRH and its analogues represent a potential possibility for the treatment of various neurological diseasses, including neurodegenerative disorders. The molecular mechanisms responsible for the beneficial effects of TRH and its analogues have not yet been fully elucidated. So far, little is known about the involvement of TRH, or its analogues, in the regulation of energy metabolism or impact on the cellular phosphoproteome. In the first part of the thesis, we focused on the study of the effect of TRH and interacting partners of TRH-R on the lateral mobility of this receptor in the membrane of the TRY-1 cell line stably expressing TRH-R labeled with yellow fluorescent protein (YFP) at the C-terminus. The results of...
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Studies of cell signaling triggered by the TRH receptor
Trubačová, Radka ; Novotný, Jiří (advisor) ; Brejchová, Jana (referee) ; Lazar, Josef (referee)
Activation of thyrotropin-releasing hormone receptor (TRH-R) signaling has an irreplaceable role in a number of cellular processes. Thyroliberin (TRH) plays an important role in the regulation of secretion of other hormones and there are also mentions of its possible antiapoptotic and neuroprotective effects. On the other hand, TRH is quickly degraded and also its other properties, such as cardiac and endocrine side effects and low lipophilicity, disadvantage the therapeutic applications of this hormone compared to its various analogues. Due to their effects on the central nervous systém, TRH and its analogues represent a potential possibility for the treatment of various neurological diseasses, including neurodegenerative disorders. The molecular mechanisms responsible for the beneficial effects of TRH and its analogues have not yet been fully elucidated. So far, little is known about the involvement of TRH, or its analogues, in the regulation of energy metabolism or impact on the cellular phosphoproteome. In the first part of the thesis, we focused on the study of the effect of TRH and interacting partners of TRH-R on the lateral mobility of this receptor in the membrane of the TRY-1 cell line stably expressing TRH-R labeled with yellow fluorescent protein (YFP) at the C-terminus. The results of...
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A study of molecular interactions of the μ-opioid receptor: the effect of biased ligands
Marková, Vendula ; Novotný, Jiří (advisor) ; Rudajev, Vladimír (referee)
G protein-coupled receptors (GPCRs) are the largest group of membrane-bound receptors. Transmission of signals into the cell interior is mediated through the interactions of these receptors with other signaling molecules. Nowadays, a great attention is devoted to biased ligands which are able to alter the conformation of the receptor in a specific way and thus distinctly affect its function. This diploma thesis was focused on a study of µ-opioid receptor (MOR), which is important in nociception. The aim of this study was to find out, how the activation of MOR by specific biased ligands (morphine, endomorphin-2 and DAMGO) affects the function and the interactions of MOR with potential molecular partners (for example G proteins or β-arrestin) A method of siRNA interference was used to knock down the following selected signaling molecules: Gαi1, Gαi2, Gαi3, Gαz and β-arrestin2. The effect of biased ligands on lateral mobility of MOR in the plasma membrane and on activity of adenylyl cyclase (AC) was examined under these conditions. We observed a possible involvement of Gαz subunit in the lateral mobility of MOR after the effect of morphine and endomorphin-2. The lateral mobility of MOR was significantly increased in cells lacking Gαi2 or Gαi3 or β-arrestin2. In this case the MOR was in inactive state....
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A study of molecular interactions of the μ-opioid receptor: the effect of biased ligands
Marková, Vendula ; Novotný, Jiří (advisor) ; Rudajev, Vladimír (referee)
G protein-coupled receptors (GPCRs) are the largest group of membrane-bound receptors. Transmission of signals into the cell interior is mediated through the interactions of these receptors with other signaling molecules. Nowadays, a great attention is devoted to biased ligands which are able to alter the conformation of the receptor in a specific way and thus distinctly affect its function. This diploma thesis was focused on a study of µ-opioid receptor (MOR), which is important in nociception. The aim of this study was to find out, how the activation of MOR by specific biased ligands (morphine, endomorphin-2 and DAMGO) affects the function and the interactions of MOR with potential molecular partners (for example G proteins or β-arrestin) A method of siRNA interference was used to knock down the following selected signaling molecules: Gαi1, Gαi2, Gαi3, Gαz and β-arrestin2. The effect of biased ligands on lateral mobility of MOR in the plasma membrane and on activity of adenylyl cyclase (AC) was examined under these conditions. We observed a possible involvement of Gαz subunit in the lateral mobility of MOR after the effect of morphine and endomorphin-2. The lateral mobility of MOR was significantly increased in cells lacking Gαi2 or Gαi3 or β-arrestin2. In this case the MOR was in inactive state....
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