National Repository of Grey Literature 43 records found  previous11 - 20nextend  jump to record: Search took 0.00 seconds. 
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....
The role of G protein-coupled receptor signaling systems in neuroprotection
Hofmannová, Adéla ; Novotný, Jiří (advisor) ; Rudajev, Vladimír (referee)
Nervous tissue, especially the brain, is very sensitive to the lack of oxygen and nutrients. Without supply of these components, the tissue endures only a few minutes and then, after the depletion of all ATP, permanent damage or even cell death occurs in neurons and glial cells. During ischemia or hypoxia, an excessive amount of the excitant neurotransmitter glutamate is released, which is neurotoxic. It causes ion imbalance and also apoptotic signaling pathways may be triggered because of the high level of intracellular calcium. Signaling through G protein-coupled receptors (GPCRs) can be involved in the establishment of increased cell resilience to hypoxic injury. Stimulation of some GPCRs, e.g. adenosine, opioid, cannabinoid and melatonin receptors, can afford neuroprotection. Activation of their cognate G proteins may lead to blockade of ion channels or affect the effector proteins, thus helping the stabilization of ion homeostasis and the inhibition of glutamate release. Moreover, some of the receptor agonists have antioxidant character, whereby they prevent the harmful action of free radicals. Neuroprotective mechanisms promote neuronal survival during harmful conditions and are also able to slow down the processes responsible for the development of neurodegenerative diseases. Key words: G...
Classification, structure and function of α-adrenergic receptors.
Makarova, Anna-Marie ; Hejnová, Lucie (advisor) ; Rudajev, Vladimír (referee)
Adrenergic receptors are ones of the most investigated receptors today. Signal transduction by adrenergic receptors is involved in stress response. Stress activates the sympathicus and the hypothalamic-pituitary-adrenal axis of autonomic nervous system. Understanding effects of this activation on adrenergic signalisation is important for affection of the "fight of flight" reaction. Affecting the activity of sympathetic nerve sis important subject of interest in pharmacology and many drugs are developed using this actions. This thesis deals with a group α-adrenergic receptors and its subtypes. One part is devoted to structure which is subject of many explorations recently especially. Next chapter focuses on signal transduction mediated by α-adrenergic receptors. The last section refers to multitude of physiologic functions induced by these receptors. Powered by TCPDF (www.tcpdf.org)
New approaches in higt-resolution shallow seismic prospection
Valenta, Jan ; Dohnal, Jiří (advisor) ; Rudajev, Vladimír (referee) ; Bárta, Jaroslav (referee)
This work deals with the application of seismic methods in high-resolution near-surface prospection. Two topics are covered in this text. The first one describes processing and application of 3D shallow seismic refraction, while the second one deals with possible methods of identification and filtration of S-waves. The processing of the 3D seismic refraction data is currently carried out mainly by means of the seismic tomography. Because the tomography method usually works with the gradient model of the subsurface, an approach to the layer-based model was sought. The solution was found in a modification of the time-term method. The time- term method was modified to handle also the lateral variations of velocity in highly heterogeneous media. REFRACT3D computer program for data processing using the time-term method was developed. The modified time-term method was successfully tested during the archaeological prospection of the Děvin Castle and during the pro- spection of the shallow subsurface of the Ostaš seismic station. The results from the time-term method were compared with the results obtained by the first arrival travel time tomography. In the case of the Děvin Castle the time-term results surpass the tomography one, while at the locality of Ostaš the tomography results are better. The imaging...
Effect of amyloid β on the function of endosomes and lysosomes
Tmějová, Monika ; Rudajev, Vladimír (advisor) ; Búran, Peter (referee)
Amyloid β peptide is produced by proteolytic processing of amyloid precursor protein. Accumulation of toxic Aβ in lysosomes and endosomes is considered to be one of the earliest signs of Alzheimer disease. Alzherimer disease was first described in 1907 by doctor Alois Alzheimer. This disease is most common in elderly people over the age of 65 and it is currently the most common cause of dementia. Although significant progress has been made in recent years, the key mechanism of formation of senile plaques and neurofibrillary tangles still remains unclear. Vesicular trafficking plays fundamental role in regulation of APP and generation of Aβ. This thesis summarizes molecular mechanisms of pathological effect of Aβ on the endolysosomal complex.
Interaction of amyloid β with neuronal membrane proteins
Manová, Blanka ; Rudajev, Vladimír (advisor) ; Černá, Barbora (referee)
Amyloid b peptide is cleaved from the amyloid precursor protein by b and γ secretases. According to the amyloid hypothesis i tis the main cause of the early pathogenetic events of Alzheimer's disease (AD) which is the most common neurodegenerative disease in the world without an effective treatment. The main pathogenesis of AD is considered to be the loss of synapses, disruption of neuronal plasticity and neurodegeneration. Amyloid b can bind directly to the membrane or mediate neuronal damage indirectly via toxic inflammatory mediators (e.g., reactive oxygen intermediates, nitric oxide and cytokines) by activating microglia and astrocytes. In addition to interacting with various membrane receptors, Ab can also bind to the cell surface directly, disrupting membrane integrity or forming selective cation channels. This thesis summarizes key interactions with membranes of synapses and mechanisms of amyloid- induced toxicity through receptors.
The importance of lipid composition of membranes for the development of Alzheimer's disease
Novotná, Natálie ; Rudajev, Vladimír (advisor) ; Hanousková, Barbora (referee)
Lipids are an essential components of cell membranes and their homeostasis plays an important role in the development of Alzheimer's disease. The aggregation and neurotoxic effects of amyloid β, mainly Aβ42, on the neural cell membrane are crucial for pathological changes in the brain tissue which leads to its degeneration and loss of cognitive functions. The complex relationship between amyloid β and lipids is also supported by fact that membrane lipids do not only support the amyloid binding to the membrane, but also they regulate the splicing of the amyloid precursor protein, therefore the biosynthesis of β amyloid. The most important binding partners of Aβ42 include gangliosides, especially the ganglioside GM1, but also sphingomyelin and cholesterol. In contrast, glycerophospholipids primarily affect the process of the protein production.
Biocompatibility of porous NCD layers with neurons
Freislebenová, Hana ; Benson, Veronika (advisor) ; Rudajev, Vladimír (referee)
Nanodiamond is currently one of the most researched materials in the field of regenerative medicine in the study of treatment of neurodegenerative diseases. Due to direct interaction of this material with nerve tissue, it needs to be biocompatible with primary neurons. Furthemore, it is desirable for the used material to induce cell adhesion and stimulate the adherent cells to regeneration. This work evaluates the biocompatibility of porous boron-doped diamond layers with the culture of primary neurons. We compared the effect of diamond surface treatment by poly- D-lysine (PDL) coating on the adhesion and prosperity of the primary neuronal culture. We found that the tested nanodiamond layers are biocompatible with the primary neuronal culture. We further conclude that the PDL coating slightly increases the rate of cell adhesion to the surface but on the other hand induces greater adhesion of glial cells than the surface without PDL coating. Key words: nanodiamond, biocompatibility, adhesion, neurons
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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