Sep 16, 2019   10:32 p.m. Ľudomila, Ľudmila
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Ing. Katarína Elefantová, PhD.
Identification number: 26866
University e-mail: katarina.turakova [at] stuba.sk
University e-mail: katarina.elefantova [at] stuba.sk
 
Vedecká pracovnice KS II.b. CSc.,PhD. - Institute of Biochemistry and Microbiology (FCFT)
Chemický laborant - Institute of Biochemistry and Microbiology (FCFT)

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Basic information

Basic information about a final thesis

Type of thesis: Dissertation thesis
Thesis title:The study of autophagy in animal cells and its relationship to changes in Ca2+ homeostasis and metabolism of complex lipids
Written by (author): Ing. Katarína Elefantová, PhD.
Department: Department of Biochemistry and Microbiology (IBM FCFT)
Thesis supervisor: doc. Ing. Boris Lakatoš, PhD.
Opponent 1:RNDr. Miroslav Barančík, CSc.
Opponent 2:Ing. Štefan Zórad, CSc.
Final thesis progress:Final thesis was successfully defended.


Additional information

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Language of final thesis:Slovak

Slovak        English

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 2.4.1.80) 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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