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Potential physiological significance of thermal preconditioning
Ptáková, Alexandra ; Novotný, Jiří (advisor) ; Benák, Daniel (referee)
Short-term exposure of cells or whole body to mild hyperthermia, known as thermal pre- conditioning, is an experimental method used to provide cytoprotection against subsequent, otherwise harmful or even lethal, stress conditions. Thermal preconditioning is relatively easily feasible and could be used to prevent various health problems. The aim of this thesis is to sum- marize current knowledge about the impact of thermal preconditioning on cells and the whole organism. The possibilities of how to perform this method effectively are described here, toge- ther with the molecular mechanisms involved in the induction of cytoprotection. Some areas where thermal preconditioning could be used are also mentioned. Key words: thermal preconditioning, hyperthermia, cytoprotection, HSP, ischemia-reper- fusion injury
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The impact of opioids on the effect of cytostatic agents on the C6 and CCF-STTG1 astrocytoma cell lines
Honc, Ondřej ; Novotný, Jiří (advisor) ; Růžička, Jiří (referee)
Despite its numerous side effects, morphine and the opioids derived from this drug, belong among the only effective options for treatment of pain linked to oncological illness. The effect of opioids on the efficiency of cytostatics in vitro has been the subject of many papers but the results are often contradictory, which could be probably caused by the great variability of experimental models and approaches. Some recent studies indicate that the consequences of activation of opioid signaling in astrocytes display certain differences from other cell types. Glioblastoma multiforme, the tumor derived from astrocytes, belong among those with the worst prognosis, mostly for the frequent resistance to cytostatics. In this thesis we focused on the effect of morphine, methadone and DADLE on the efficiency of cytostatics of temozolomide, doxorubicin and vincristine on the cell lines C6 and CCF-STTG1 derived from glioblastomas. Also, we examined the effect of the above mentioned opioids on the level of oxidative cellular stress and using N-acetylcysteine, a ROS scavenger, we verified the role of oxidative stress in cellular systems activated by the effect of the mentioned opioids on the efficiency of cytostatics. We also assessed opioid receptors and the receptor TLR4 in the examined cell lines. The...
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Compartmentalization of the beta-adrenergic signaling system in cardiac cells: the effect of hypoxia
Karlovská, Ivana ; Novotný, Jiří (advisor) ; Nováková, Olga (referee)
The aim of this thesis was to study the changes that occur in cell line H9c2 after exposure to an oxygen level reduced to 2 % for 24 hours. We monitored changes in compartmentation of chosen members of β-adrenergic signaling system. We found an increase in expression of β1AR and β2AR. Only β2AR showed change in compartmentation after hypoxia, as they relocate from membrane rafts to non-rafts fractions of membrane. AC also showed an increase of expression and was located in membrane rafts. The next aim of this work was to monitore apoptotic markers to determine whether there are activated pro-apoptotic or anti-apoptotic signals under chosen conditions of hypoxia. There was an increase in expression of both pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2. We compare ratios of Bcl-2 to Bax and we found that there is a bigger increase in protein Bax expression. Another apoptotic marker, caspase 3, was tested and we also found that there was an increase in expression of caspase 3 in cells after hypoxia. Furthermore, we studied possible activation of kinase signaling pathways that may contribute to protective effects of hypoxia. Expression of Akt and ERK kinases was increased after hypoxia, but we did not confirm activation by phosphorylation of these kinases. Levels of phosphorylated Akt...
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A study of signaling and cytoprotective potential of cannabinoid GPR55 receptors in PC12 cells
Pavluch, Vojtěch ; Novotný, Jiří (advisor) ; Ostašov, Pavel (referee)
At the end of the 20th century it was known that cannabinoid drugs interact with two receptors, CB1 and CB2. Subsequent pharmacological studies have confirmed that there are other receptors interacting with cannabinoids. GPR55 is a transmembrane G protein coupled receptor, which together with the receptor GPR18 and GPR119 belong to a group of new cannabinoid receptors and is involved in the function of the endocannabinoid system. In addition to some of cannabinoid substances, it is stimulated primarily phospholipid lysofosfatidylinositolem. LPI-dependent signaling GPR55 plays an important role in the regulation of many physiological and pathological processes, such as pain, inflammation, cell proliferation, or endothelial function. It was found that LPI confers tolerance to ischemic brain damage and has a cytoprotective effect on the pyramidal cells. The aim of the study was to determine whether the application of five ligands induce phosphorylation of protein kinase ERK 1/2, Akt and activate the GTPase RhoA and whether activation of the receptor GPR55 has cytoprotective effect in model cell line PC12, in which hypoxic conditions were simulated by adding CoCl2. For working methods were used SDS-PAGE, Western bloting and colorimetric measurement. Pharmacological studies in recent years have shown...
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