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Uptake of heavy metals - the role of the root system
Homola, Adam ; Tylová, Edita (advisor) ; Mašková, Petra (referee)
Heavy metals are important soil pollutants and pose a significant risk to plants under certain conditions. These include some essential microelements (Fe, Zn, Mn, Mo, Cu, Ni) and toxic metals (e.g. Cd, As, Pb, Hg). Essential microelements have important functions in plants, and are mainly involved in plant metabolism as cofactors of enzymes. Toxic metals have no function, yet they enter the plant in varying degrees from the environment and cause toxicity. However, excessive concentrations of essential metals in the plant also have negative effects and plants have different mechanisms to counteract these negative effects. The bachelor thesis focuses mainly on the uptake of heavy metals from the soil by the root, which is achieved by membrane transporters. It also discusses several mechanisms involved in defence against heavy metal toxicity, not only in terms of regulating uptake, but also after heavy metals have entered plant bodies. These mechanisms are an important aspect of hyperaccumulation, which is also included in this thesis. Hyperaccumulators use these mechanisms on a completely different scale than non-hyperaccumulators, which allows hyperaccumulators to live in environments where heavy metal concentrations are high, making them completely different from each other. The properties of...
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Molecular mechanism of animal cells adaptation on hyperosmotic induced stress
Novotná, Jana ; Vávra, Jiří (advisor) ; Převorovský, Martin (referee)
Various types of cells animal tissues consist of need to adapt to intracellular as well as extracellular osmotic changes in order to maintain homeostasis. Hypertonicity (increased osmolarity) is one of the factors activating complex cellular reactions. In order to manage such stress, a cell needs to incorporate regulation pathways that can either regulate ion transporters through WNK kinases or activate gene expression of transporters of compatible osmolytes through the transcription factor TonEBP/NFAT5. Physiologically exposed to hypertonic conditions are cells in renal medulla, cartilage, inner ear tissues, in specialised neurons or buccal epithelium. This work includes basic and current knowledge about the adaption of cells to increased osmolarity of outer environment. Key words: Hyperosmolarity, osmotic stress, TonEBP/NFAT5, WNK kinases, NF-κB, HSP70
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In vitro and ex vivo study of drug-drug interactions of antivirals on intestinal membrane transporters
Halodová, Veronika ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Halodová Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: In vitro and ex vivo study of drug-drug interactions of antivirals on intestinal membrane transporters Tenofovir (TFV) is the first-line agent in the treatment of hepatitis B virus (HBV) infection for patients aged over 12 years and one of the first-line choices for the combination antiretroviral therapy (cART) of infections caused by human immunodeficiency virus (HIV). Two commercially available prodrugs have been developed for oral administration of TFV, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF). These prodrugs increase TFV membrane permeability and oral bioavailability. One of the factors that can affect the bioavailability of orally administrated drugs is active transport mediated by efflux transporters, mainly by P-glycoprotein (ABCB1, P-gp) and Breast cancer resistance protein (ABCG2, BCRP). It has been already proved that TDF and TAF are substrates of both of these transporters. The goal of this diploma thesis was to use in vitro and ex vivo models of intestinal barrier to assess the impact of the efflux transporters on TDF and TAF transport in the intestine and on their...
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In vitro and ex vivo study of drug-drug interactions of antivirals on intestinal membrane transporters
Halodová, Veronika ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Halodová Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: In vitro and ex vivo study of drug-drug interactions of antivirals on intestinal membrane transporters Tenofovir (TFV) is the first-line agent in the treatment of hepatitis B virus (HBV) infection for patients aged over 12 years and one of the first-line choices for the combination antiretroviral therapy (cART) of infections caused by human immunodeficiency virus (HIV). Two commercially available prodrugs have been developed for oral administration of TFV, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF). These prodrugs increase TFV membrane permeability and oral bioavailability. One of the factors that can affect the bioavailability of orally administrated drugs is active transport mediated by efflux transporters, mainly by P-glycoprotein (ABCB1, P-gp) and Breast cancer resistance protein (ABCG2, BCRP). It has been already proved that TDF and TAF are substrates of both of these transporters. The goal of this diploma thesis was to use in vitro and ex vivo models of intestinal barrier to assess the impact of the efflux transporters on TDF and TAF transport in the intestine and on their...
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In vitro study of drug-drug interactions of HIV protease inhibitor darunavir on efflux ABC transporters
Bezděková, Dominika ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Dominika Bezděková Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: IN VITRO STUDY OF DRUG-DRUG INTERACTIONS OF HIV PROTEASE INHIBITOR DARUNAVIR ON EFFLUX ABC TRANSPORTERS Abstract: Darunavir is a drug used in the therapy of HIV belonging to the group of protease inhibitors. These protease inhibitors are used as a part of the combination antiretroviral therapy. For the increase of bioavailability, darunavir is always used in combination with ritonavir or cobicistat. As the CYP3A4 and ABCB1 (P-glycoprotein) transporter substrate, darunavir is a drug with a high potential to drug interactions. Considering the amount of adverse effects that can be caused by darunavir, it is necessary to know these drug interactions for the safety of therapy. Inhibition of the intestinal ABCB1 by the co-administrated drugs could also lead to the increased bioavailability of darunavir and to reduction of frequency of administration leading to a cheaper therapy. This thesis studies the drug-drug interactions of darunavir with in vitro methods using two cell lines - MDCKII and Caco-2 cells. The results from the transport of darunavir across the MDCKII cell monolayer indicates that darunavir is a ABCB1...
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The structure and function of transmembrane proteins ABCG2
Vávra, Jiří ; Mančíková, Andrea (advisor) ; Novotný, Marian (referee)
ABCG2 (ABCP/MXR/BCRP) transporters create homodimers through the plasma membrane. They play an important role in transmembrane transport of a wide spectrum of biological substrates. They are essential for renal, intestinal, placental and haematoencephalic barrier function. In particular they perform an excretory function, protect cells against toxic compounds and xenobiotic cumulation. They are also involved in metabolic regulation of stem cells. This bachelor thesis summarizes information about ABCG2 protein function, their physiological role in humans and other mammals. Keywords: ABCG2, BCRP, membrane transporters, multidrug resistention (MDR), ATP binding cassette family (ABC)
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Involvement of AtKT/HAK/KUP high-affinity transporters in plant K+ and Cs+ uptake
Šustr, Marek ; Tylová, Edita (advisor) ; Maršík, Petr (referee)
Potassium is essential macroelement and large amount of potassium is taken up by plants, because it's the major osmotic of plant cell. Due to various potassium availability in different kinds of soil, plants have evolved transport system that can maintain sufficient K+ uptake between several orders of magnitude of potassium concentration. In Arabidopsis thaliana mechanism of K+ acquisition is well understood and it's known that AtHAK5 is mainly involved in K+ uptake in its very low concentrations. AtHAK5 belongs to KT/HAK/KUP family that consist 13 members in A. thaliana. There's known function for some members for example in auxin transport in root tip (TRH1) or in K+ efflux in stomatal closure (KUP6). In this thesis possible involvement of yet unstudied transporters KUP5, KUP7, KUP9 and KUP10 in K+ acquisition and homeostasis in A. thaliana was investigated. In vitro cultivation showed that kup9 mutant has very short lateral roots in K+ deficiency. On the other hand kup5 mutant showed significantly higher dry weight in K+ deficiency than Col-0. Kup9 phenotype was successfully replicated in subsequent cultivations and anatomy of lateral root apical meristems was investigated. Root tips of kup9 were differently organized in K+ deficiency and they showed signs of early termination of meristems. To...
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