Twórca instytucjonalny:

Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN ; Uniwersytet Warszawski

Współtwórca:

Szewczyk, Adam (1960- ) : Supervisor ; Bauer, Tomasz : Supervisor

Wydawca:

Instytut Biologii Doświadczalnej im. M. Nenckiego PAN

Miejsce wydania:

Warszawa

Opis:

189 pages : illustrations ; 30 cm ; Bibliography ; Summary in English

Instytucja nadająca tytuł:

Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN

Typ obiektu:

Thesis

Abstrakt:

Potassium channels present in the inner mitochondrial membrane are involved in the regulation of many cellular processes. Activation of the mitochondrial large conductance calcium regulated potassium channel (mitoBKCa) protects the cardiomyocytes and brain cells during ischemia/reperfusion. On the other hand, inhibition of the mitochondrial Kv1.3 channel activity increases the cancer cells death. The experiments described in this dissertation focused on electrophysiological and biochemical studies on identification and characterization of the mitochondrial BKCa channels in selected model cell lines and the search for new low molecular weight modulators (activators and inhibitors) of this channel activity. Characterization of new mitoBKCa channel modulators could contribute to a better understanding of the mechanisms leading to both cytoprotection and cell death.The aim of this dissertation was to identify the mitochondrial BKCa channel in human bronchial epithelial cells and to compare the activity of this channel with the exogenous mitochondrial VEDEC isoform of BKCa channel.The first part of the dissertation presents the results of electrophysiological studies using the patch-clamp technique, which allowed to characterize the mitoBKCa channel in bronchial epithelial cells. It is worth noting that this is the first description of a mitochondrial potassium channel in this type of cell in the literature. Then, experiments on the properties of the mitochondrial VEDEC isoform of the BKCa channel were described in the new developed research model HEK293-BK_DEC cells.In the next part of this dissertation, the influence of low molecular weight synthetic compounds and of plant origin on the activity of the described mitoBKCa channels was examined. One of the investigated naringenin derivatives, 7-O-prenyl-naringenin, has been shown to activate the mitochondrial channel that occurs endogenously in bronchial epithelial cells and exogenously in HEK293-BK_DEC cells. It was also found that another derivative of flavonoids - chalcone 4 ', 5, 7-tri-O-methyl-naringenin completely inhibits the activity of both tested channels. Experiments were also carried out to identify new potassium channel inhibitors with a structure similar to the channel inhibitor - paxilline. Selected compounds reduced the open probability of the mitoBK_DEC channel but not as effectively as the commonly used paxilline.In conclusion, this dissertation presents the new localization of the mitochondrial BKCa channel in bronchial epithelial cells and investigates the properties of the VEDEC isoform of this channel in the newly developed HEK293-BK_DEC cell model. The effect of potential new modulators, synthetic and natural compounds on the activity of mitoBKCa channels are also presented

Szczegółowy typ zasobu:

PhD Dissertations

Identyfikator zasobu:

oai:rcin.org.pl:238045

Źródło:

IBD PAN, call no. 20186

Język:

pol

Język streszczenia:

eng

Digitalizacja:

Nencki Institute of Experimental Biology of the Polish Academy of Sciences

Lokalizacja oryginału:

Library of the Nencki Institute of Experimental Biology PAS

Dostęp:

Open