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National Repository of Grey Literature 2 records found  Search took 0.00 seconds. 
Influence of lipid composition and model peptides on lateral organization of lipid layers
 Veľas, Lukáš ; Heřman, Petr (advisor) ; Malínský, Jan (referee)
Oxidized phospholipids (OxPLs) are known to be present in living organisms due to oxidative stress. However, the physiological function of OxPLs is still not fully understood. They have been shown to be present in many inflammatory diseases such as atherosclerosis and neurodegenerative diseases like Parkinson's and Alzheimer's disease. In this work we present the influence of two truncated OxPLs on the lateral heterogeneity of a model lipid membrane. Specifically, we studied the effect of 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3- phosphocholine (POVPC) and 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC) on the formation of nanodomains present in giant unilamellar vesicles containing 1,2- dioleoyl-sn-glycero-3-phosphocholine (DOPC), cholesterol and sphingomyelin. Only few techniques are capable of detecting nanometer-sized domains in the membrane with high resolution. Time resolved Förster resonance energy transfer (TR-FRET) combined with Monte Carlo (MC) simulations provide a strong tool not only to detect lateral heterogeneities but also characterize them with the resolution of 2 nm. Profound effects on the nanodomain size were observed in the presence of both studied OxPLs and differences were detected, as PGPC with a carboxylic group drives formation of larger nanodomains than POVPC...
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Monitoring the effect of medically important drugs on activity of human P-glycoprotein using fluorescent probes
 Veľas, Lukáš ; Gášková, Dana (advisor) ; Sigler, Karel (referee)
One of the main causes of failure in cancer treatment when using chemotherapy is the phenomenon of multidrug resistance - MDR. The most important protein mediating MDR in human cells is P-glycoprotein. The main goal of this thesis was the modification of fluorescent method - developed for studying yeast MDR pumps at the Department of Biophysics at the Institute of Physics of Charles University - to study the activity of P-glycoprotein in human tumor cells. The fluorescent method is based on the use of redistribution potentiometric probe diS-C3(3) which we found to be a substrate of P-glycoprotein. The optimalization of the method (experimental window) allowed sensitive monitoring of changes in the activity of P-glycoprotein caused by the effect of its several known inhibitors/substrates: oligomycin, amiodarone, verapamil, vinblastine, ketoconazole, itraconazole and FK506. New important results regarding the effect of these medically significant drugs on human cells were obtained. The developed method will undoubtedly be of great benefit in the search for new effective inhibitors and the study of their mechanisms in the future.
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