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TOR signalling in yeast
Šimek, Jan ; Palková, Zdena (advisor) ; Španielová, Hana (referee)
TOR ("Target of rapamycin") protein, a highly conserved Ser/Thr protein kinase, is a central component of signalling network that controls cell growth in diverse eukaryotic organism, ranging from yeast to man. TOR proteins were first identified in yeast Saccharomyces cerevisiae in 1991 as the targets of the antifungal and immunosupressive agent rapamycine. In contrast to most eukaryotes, yeast contains two TOR homologues , Tor1p and Tor2p. These proteins are components of multiprotein complexes TORC1 and TORC2. TORC1 is specifically inhibited by rapamycine and controls cell growth in response to quality of the available nutrients. TORC2, which is insensite to rapamycine, regulates actin polymerization, sphingolipid biosynthesis and endocytosis. This work is focused on description of both TOR complexes, especially on downstream and upstream regulation of TORC1. Powered by TCPDF (www.tcpdf.org)
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The role of autophagy in apoptosis induction by fatty acids in pancreatic beta cells.
Žigová, Ivana ; Němcová, Vlasta (advisor) ; Truksa, Jaroslav (referee)
Type 2 diabetes mellitus represents a metabolic disease reaching epidemic dimensions in the 21st century. Fatty acid-induced apoptosis of pancreatic β-cells significantly contributes to its pathogenesis. Saturated fatty acids (FAs) are strongly cytotoxic for β-cells, whereas unsaturated FAs are well tolerable by β-cells, they are even able to inhibit proapoptotic effects of saturated FAs when co-incubated. According to recent studies, FAs-induced apoptosis in pancreatic β-cells is partly regulated by autophagy, a catabolic process involved in the degradation and recyclation of cell components in lysosomes. The aim of this diploma thesis was to contribute to the clarification of the role of autophagy in FAs-induced apoptosis regulation. We induced apoptosis in human pancreatic β- cell line NES2Y by 1 mM stearic acid (SA) and inhibited it with 0.2 mM oleic acid (OA) co- incubated with SA. We revealed, that the saturated SA used in apoptosis-inducing concentration simultaneously inhibits the autophagic flux in pancreatic NES2Y cell line. When SA is co- incubated with unsaturated OA in concentration sufficient for inhibition of proapoptotic effect of SA, OA is also able to inhibit the block of autophagy induced by the effect of SA. Application of unsaturated OA alone in this concentration did not...
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The role of mTOR signalling pathway in neural differentiation of stem cells
Šintáková, Kristýna ; Jendelová, Pavla (advisor) ; Dráber, Peter (referee)
Spinal cord injury is a very serious, complex, and life changing injury for which today's medicine still does not have an efficient treatment. It is only possible to mitigate the consequences of this injury and the pathological processes associated with it. Neural stem cell transplantation has immunosuppressive effects in the pathology of spinal cord injury and promotes regeneration. mTOR kinase is a member of the crucial intracellular PI3K/Akt/mTOR signalling pathway, making it a suitable target for therapeutic intervention and immunosuppressants such as rapamycin. mTOR signalling is important for neural stem cells and in the pathology of spinal cord injury. The aim of this study was to investigate the role of the mTOR pathway in differentiation of stem cells into neuronal phenotype. Rapamycin was applied to in vitro culture of neural progenitors. Immunocytochemistry and immunoblotting techniques were used to study the effect of this inhibition on the cell phenotype and on the activity of the mTOR pathway. Using the rat model of spinal cord injury in vivo, immunohistochemistry and immunoblotting techniques were used to evaluate the impact of rapamycin inhibition on the mTOR pathway, autophagy, and cytokine production by cells in the damaged tissue. The results show that the mTOR pathway plays role...
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Crosstalks between nitrogen metabolism, the TOR pathway and the metabolism of lipids
Grulyová, Michaela ; Převorovský, Martin (advisor) ; Maršíková, Jana (referee)
Cells coordinate their metabolism based on various factors, for example nitrogen availability. The TOR pathway is an important regulator of nitrogen metabolism, it has a role in sensing intracellular amino acids status, and it controls especially cell growth, protein synthesis, proliferation and cell survival. However, it has been shown that the TOR pathway also controls lipid biosynthesis and lipid accumulation through various mechanisms in response to nitrogen availability. Although the TOR pathway is well conserved among the eukaryotic organisms, its outcomes differ diametrically when it comes to the lipid accumulation. This essay provides some insides into the mechanisms of regulation of the lipid metabolism by the TOR pathway.
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TOR signalling in yeast
Šimek, Jan ; Palková, Zdena (advisor) ; Španielová, Hana (referee)
TOR ("Target of rapamycin") protein, a highly conserved Ser/Thr protein kinase, is a central component of signalling network that controls cell growth in diverse eukaryotic organism, ranging from yeast to man. TOR proteins were first identified in yeast Saccharomyces cerevisiae in 1991 as the targets of the antifungal and immunosupressive agent rapamycine. In contrast to most eukaryotes, yeast contains two TOR homologues , Tor1p and Tor2p. These proteins are components of multiprotein complexes TORC1 and TORC2. TORC1 is specifically inhibited by rapamycine and controls cell growth in response to quality of the available nutrients. TORC2, which is insensite to rapamycine, regulates actin polymerization, sphingolipid biosynthesis and endocytosis. This work is focused on description of both TOR complexes, especially on downstream and upstream regulation of TORC1. Powered by TCPDF (www.tcpdf.org)
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The role of autophagy in apoptosis induction by fatty acids in pancreatic beta cells.
Žigová, Ivana ; Němcová, Vlasta (advisor) ; Truksa, Jaroslav (referee)
Type 2 diabetes mellitus represents a metabolic disease reaching epidemic dimensions in the 21st century. Fatty acid-induced apoptosis of pancreatic β-cells significantly contributes to its pathogenesis. Saturated fatty acids (FAs) are strongly cytotoxic for β-cells, whereas unsaturated FAs are well tolerable by β-cells, they are even able to inhibit proapoptotic effects of saturated FAs when co-incubated. According to recent studies, FAs-induced apoptosis in pancreatic β-cells is partly regulated by autophagy, a catabolic process involved in the degradation and recyclation of cell components in lysosomes. The aim of this diploma thesis was to contribute to the clarification of the role of autophagy in FAs-induced apoptosis regulation. We induced apoptosis in human pancreatic β- cell line NES2Y by 1 mM stearic acid (SA) and inhibited it with 0.2 mM oleic acid (OA) co- incubated with SA. We revealed, that the saturated SA used in apoptosis-inducing concentration simultaneously inhibits the autophagic flux in pancreatic NES2Y cell line. When SA is co- incubated with unsaturated OA in concentration sufficient for inhibition of proapoptotic effect of SA, OA is also able to inhibit the block of autophagy induced by the effect of SA. Application of unsaturated OA alone in this concentration did not...
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