Persons at STU
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Basic information about a final thesisAdditional informationAdditional information about the final thesis follows. Click on the language link to display the information in the desired language.
|Language of final thesis:||Slovak|
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|Title of the thesis:||The study of autophagy in animal cells and its relationship to changes in Ca2+ homeostasis and metabolism of complex lipids|
|Summary:||Glucosylceramide (GlcCer) is an essential glycosylated lipid found in oragnisms ranging from fungi to mammals. It is composed of a hydrophilic beta-linked glucose and a hydrophobic ceramide, with a predominant content of sphingosine in mammals (d18:1). GlcCer is a precursor of a large scale of different glycosphingolipids. The presence of UDP-glucose and activity of glucosylceramide synthase (GCS, EC 220.127.116.11) is essential for GlcCer synthesis. GlcCer-based sphingolipids have been identified as important mediators of a variety of cellular functions. Their disequilibrium leads to pathological process development and may induced several diseases progression. Therefore, design of GCS inhibitor represents an important topic for pharmaceutical research. P-glycoproetein (Pgp) expression in neoplastic cells is known to reduced cell sensitivity to cytotoxic Pgp substrates. A member of ABC transporter family, Pgp, represents the most frequently described membrane efflux pump Its expression in neoplastic cells is responsible for MDR. Several lines of evidence indicate that the expression of Pgp is often accompanied by enhanced activity of GCS and leads to enhanced resistance of cytostatic drugs. In mice leukemia L1210 Pgp-possitive cells resistant to vincristine, has reduced levels of UDP-glucose. The reduced availibilty of UDP-glucose was reflected as enhanced sensitivity of Pgp-possitive cells to exogenous ceramides. We aimed to study effects of known inhibitor of GCS and their newly synthesised potential analogues on programed cell death of mice thymocytes and leukemic L1210 cells, Ca2+ transport and activity of GCS in vitro. The key factors influencing the effect of PPMP analogues were their concentration, chemical structure and incubation time. Derivatives were able to change calcium transport alreadyafter 15 min of cultivation, but their effects on cell viability were manifested at least after 12 h of cultivation. Four from eleven studied compounds affected GCS activity, but without correlation with data relating to effects on Ca2+ transport and cell viability.|
|Key words:||mice thymocytes, L1210 cells, glucosylceramide synthase, P-glycoprotein, cell death|
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