National Repository of Grey Literature 107 records found  previous11 - 20nextend  jump to record: Search took 0.01 seconds. 
The role of caspase 2 in apoptosis induction in tumor cells.
Schmiedlová, Martina ; Kovář, Jan (advisor) ; Horníková, Lenka (referee)
Within the cell, caspase-2 probably fulfills several functions. Caspase-2 can be involved in apoptosis induction, DNA repair as well as cell cycle regulation. Caspase-2 has the character of initiator and also executioner caspase. A stimulus for caspase 2 activation can be oxidative stress or DNA damage. Caspase-2 is activated by cleavadge during an interaction with protein complexes. One of protein complexes,i.e. PIDDosome, is made of protein PIDD, RAIDD and pro-caspase-2. Withine the PIDDosome, caspase-2 is activated. Activated caspase-2 occures in a short S form and in long L form. L form of caspase-2 has proapoptotic effects and S form of caspase-2 has antiapoptotic effects. Caspase-2S has been only detected on mRNA level but not on protein level. The main role of caspase-2L is apoptosis induction in normal and tumor cells. Caspase-2 in tumour cells is activated by extrinstic as well as intristic apoptotic pathway. Apoptosis induction by caspase-2 is for example studied in connection with breast cancer treatment with taxanes. Caspase-2 ability of apoptosis induction in cancer cells independently of p53 protein is employed in cancer treatment including overcoming the resistance to apoptosis induction which is based on loosing p53 activity. Caspase-2 is involved in apoptosis induction by different...
Regulation of VLDL production in the liver
Jirátová, Markéta ; Kovář, Jan (advisor) ; Cahová, Monika (referee)
The aim of this thesis is to summarize current knowledge about VLDL (very low density lipoprotein) assembly. In the first part of this thesis basic characteristics of lipids and lipoproteins are described. Lipids are the most favourable source of energy for animals. Lipoproteins are the macromolecular complexes that transport hydrofobic lipids in plasma. According to their density, they are classified to five groups: chylomicrons, VLDL, IDL, LDL, HDL. Second part of this thesis is focused on the apolipoproteins - structural peptide components of lipoproteins. The characteristics and functions of major apolipoprotein classes are explained with the main focus on apolipoproteins B that have an important role in VLDL assembly. The process of VLDL assembly is described in detail in the third part of the thesis. VLDL assembly consists of two steps. Pre-VLDL and lipid droplet are synthetized independently in the first step, for which apolipoprotein B-100 and microsomal triglyceride transfer protein (MTP) are essential. Second step is the fusion of pre-VLDL with the lipid droplet. ADP-ribosylation factor 1 (ARF1) and phospholipase D (PLD) are the essential components in the second step. Also apolipoprotein E, apolipoprotein A-V and acyl-coenzym A:cholesterol acyl transferasa 2 (ACAT2) are important. VLDL...
Serum markers of cholesterol 7α hydroxylase activity
Bohdanecká, Alena ; Leníček, Martin (advisor) ; Kovář, Jan (referee)
Cholesterol 7-hydroxylase (CYP7A1) is the rate limiting enzyme of the classical pathway of bile acid (BA) synthesis, which catabolizes approximately half of cholesterol in man. Determination of CYP7A enzymatic activity is a key subject of lipid metabolism research. Direct determination of CYP7A1 activity in hepatic biopsy is mostly not allowed for ethical reasons, so indirect methods are used with serum markers such as 7α-hydroxy-4-cholestene-3- one (C4). The first, methodical aim of the work was to convert the introduced HPLC method for the determination of C4 to LC-MS in order to increase the sensitivity. We focused on the solid phase extraction step, adjusting the composition and volumes of the washing and elution solution. By converting the method from HPLC to LC-MS, the sensitivity was increased approximately 7 times (LD = 1.39 ng/ml). In the second, clinical part of our work, we attempted to confirm the preliminary results of our laboratory on the distribution of C4 in lipoprotein fractions (LPP) in order to find parameter that would correlate with CYP7A1 activity better than C4 level itself. Preliminary results (performed in healthy individuals) showed that most of C4 is carried on HDL, and that the C4 distribution within LPP fractions is similar among examined subjects. We repeated the...
Gilbert Syndrome.
Šimáková, Eva ; Kuklík, Miloslav (advisor) ; Kovář, Jan (referee)
This thesis focuses on finding a possible link between genotype typical for Gilberts syndrome and specific diseases. It nvestigates a possible protective effect of the 7TA allele. It explains the origin, symptoms, pathology of this syndrome and its consequences for clinical medicine. Possible protective effect of this polymorphic mutation including reduced incidence of vascular diseases (myocardial infarction, stroke, atherosclerosis, etc.). is discussed. Reduced oxidative stress in hyperbilirubinaemia can be the mechanism behind. The work was carried out in the co-operation with the GENVIA laborator.
Role of the mitochondrial pathway in apoptosis induction by taxanes in breast cancer cells
Schmiedlová, Martina ; Kovář, Jan (advisor) ; Anděra, Ladislav (referee)
Apoptosis represents one of the cell death mechanisms which is realized after the application of taxanes in breast cancer cell lines. Apoptosis induction can be principally triggered either by outer or inner pathway. The aim of the diploma thesis is to contribute to the elucidation of role and mechanisms of the inner mitochondrial pathway of apoptosis induction after taxane application (paclitaxel and SB-T-1216) employing a model of breast carcinoma cell lines SK- BR-3 (nonfunctional p53, functional capase-3) and MCF-7 (functional p53, nonfunctional caspase-3). Specifically, we tested the effect of both employed taxanes on mitochondrial membrane potential, ROS level and the expression and localization of proteins regulating inner mitochondrial pathway. Taxane application resulted in mitochondrial membrane dissipation in SK-BR-3 cell line. However, this was not shown in MCF-7 cell line. We found no changes in Bax and Smac/DIABLO expression after taxane application in both tested cell lines. There was a decrease of Bid expression after taxane application in SK-BR-3 line, but not in MCF-7 line. Taxane application did not lead to the translocation of Bax and Bid (tBid) proteins from cytosol to mitochondria in both tested cell lines. Similarly, there was no Smac/DIABLO release from mitochondria to...
Molecular mechanisms of apoptosis induced by photodynamic activation in cancer cells
Moserová, Irena ; Králová, Jarmila (advisor) ; Kuželová, Kateřina (referee) ; Kovář, Jan (referee)
Photodynamic therapy (PDT) is a treatment modality for cancer. It combines selective accumulation of chemical compounds, called photosensitizers (PS), with light to irreversibly damage cancer cells via oxidative stress. The main goal of this thesis was to study photosensitizers represented by a unique group of newly synthesized porphyrin derivatives with glycol chain substitution. Glycol-functionalized porphyrins containing one to four low molecular weight glycol chains that are linked via ether bonds to the meta-phenyl positions of meso-tetraphenylporphyrin (mTPP(EG)1-4) were compared with fluorinated (pTPPF(EG)4) and nonfluorinated (TPP(EG)4) derivatives having glycol chains in para-phenyl positions. The cellular uptake and photodynamic activity was significantly dependent on terminal groups of the glycol substituent. Hydroxy glycol porphyrins, in contrast with methoxy glycol porphyrins, exhibited efficient intracellular transport and high induction of apoptosis in tumor cell lines in vitro. After initial testing effective prototype hydroxy ethylene glycol derivatives were selected and analyzed in detail. Para derivatives pTPP(EG)4 and pTPPF(EG)4 accumulated mainly in lysosomes whereas meta derivatives mTPP(EG)1-4 in the endoplasmic reticulum (ER). Position of ethylene glycol chain on the...
Mechanisms of invasiveness and transcription regulation in cancer cells
Tolde, Ondřej ; Folk, Petr (advisor) ; Kovář, Jan (referee) ; Brdička, Tomáš (referee)
The mechanisms of invazivity and regulation of transcription of cancer cells Cancer originates in cells that overcome the control mechanisms of the organism. Cancer cells can be eventually released from the site of origin and spread through tissues. Cancer cells can acquire certain mechanisms that enable them to more effectively invade surrounding tissue or layers of other cells. The research on the migration of cancer cells is important for the understanding of the origin and spreading of metastases and consequently for anticancer therapy. In my Ph.D. work, I participated in the research of the properties of invasive metastatic cells. We compared non-invasive rat sarcoma cell line with a higly metastatic cell line derived from it. We showed that cells of the invasive cell line use amoeboid mode of migration, have upregulated Rho/ROCK signaling, and have accumulated actin and myosin at the leading edge. It is at the leading edge where the cells generate their traction forces. Cells of non-invasive cell line use mesenchymal mode of migration and generate forces mainly at their retracting end. We also compared two breast cancer cell lines derived from a single carcinoma. We showed that the more invasive cell line, derived from its parental line by neoplastic transformation, displayed elevated cytoskeletal...
Molecular mechanisms of apoptosis induction in tumor cells
Koc, Michal ; Kovář, Jan (advisor) ; Červinka, Miroslav (referee) ; Haškovec, Cedrick (referee)
V. Závěr Tato práce se zaměřila na studium procesů uplatňujících se v indukci apoptosy různými faktory. V našem případě jsme indukovali buněčnou smrt u nádorových buněk deprivací železa, klinicky používanými taxany (paclitaxel, docetaxel) a nově syntetisovanými fotosensitivními látkami. Z presentovaných publikací jsme získali tyto závěry. (1) Studie týkající se indukce apoptosy deprivací železa prokázaly účast odlišných signálních drah vedoucí k indukci apoptosy u myších a lidských nádorových buněk. V obou případech byla použita B lymfomová buněčná linie citlivá k deprivaci železa. U myších buněk jsme popsali významnou část apoptotické signální dráhy u 38C13 buněk sensitivních k indukci apoptosy deprivací železa. Deprivace železa u těchto buněk vede k translokaci proapoptotického proteinu Bax z cytosolu na mitochondrie, která je následována zhroucením mitochondriálního membránového potenciálu v důsledku porušení integrity vnější mitochondriální membrány, uvolněním cytochromu c z mitochondrií, aktivací kaspasy 9 a následnou aktivací kaspasy 3. U lidských buněk jsme taktéž zaznamenali indukci apoptosy deprivací železa, avšak charakterem mechanismu odlišnou od apoptosy popsané u myších 38C13 buněk. V případě lidských Raji buněk sensitivních k indukci apoptosy deprivací železa docházelo pouze k aktivaci kaspasy...
Mechanisms of apoptosis induction and inhibition by fatty acids in pancreatic β-cells
Šrámek, Jan ; Kovář, Jan (advisor) ; Brunerová, Ludmila (referee) ; Šeda, Ondřej (referee)
Recently, diabetes mellitus type 2 (DMT2) represents one of the most important metabolic diseases according to its incidence and economic impacts. One of the main reasons of this diesease is loss of function and viability of pancreatic β-cells due to the effect of increased levels of saturated fatty acids (FAs). Unsaturated FAs are better tolerated by β-cells. They are even capable of inhibiting detrimental effects of saturated FAs. Molecular mechanisms of apoptosis induction in pancreatic β-cells by saturated FAs as well as mechanisms of inhibition of this induction by unsaturated FAs are not completely elucidated. The main aim of this study was to contribute to elucidation of these mechanisms. Concerning human pancreatic β-cell line NES2Y we demonstarted: (1) Activation of caspase-2 by stearic acid (SA), in apoptosis inducing concentration (1 mM), is not crucial for the process of apoptosis induction. However, this caspase modulates SA-induced endoplasmic reticulum (ER) stress pathways. (2) SA (1 mM) activates the p38 MAPK signaling pathway and inhibits the ERK signaling pathway. Inhibition of the ERK signaling pathway is probably a consequance of the p38 MAPK pathway activation. However, p38 MAPK is not very likely crutial for the apoptosis induction by SA. Unsaturated oleic acid (OA, 0.2 mM) is able to...

National Repository of Grey Literature : 107 records found   previous11 - 20nextend  jump to record:
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