Dissertationen zum Thema „Lipid transporters“
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Raggers, René John. „Lipid translocation by multidrug transporters“. [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2001. http://dare.uva.nl/document/60218.
Der volle Inhalt der QuelleAlrosan, Amjad. „Characterization of Interacting Partners of ABC Lipid Transporters“. Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/22999.
Der volle Inhalt der QuelleCharalambous, Kalypso Nicola. „The effect of lipid bilayer composition on small multidrug resistance transporters“. Thesis, University of Bristol, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432740.
Der volle Inhalt der QuelleWei, Liang Shen. „Drug and lipid interactions on the ABC transporters ABCG1 and MsbA“. Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609340.
Der volle Inhalt der QuelleFrangos, Zachary Joseph. „Investigating the molecular mechanism of bioactive lipid inhibitors of GlyT2“. Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/28029.
Der volle Inhalt der QuelleAleidi, Shereen Mohammad Suleimann. „Characterization of the Post-Translational Regulation of the ABCA1 and ABCG1 Lipid Transporters by E3 Ligases“. Thesis, The University of Sydney, 2016. http://hdl.handle.net/2123/15477.
Der volle Inhalt der QuelleChantemargue, Benjamin. „In silico investigation of xenobiotic interactions with lipid bilayers and ABC membrane transporters, the case of ABCC4/MRP4“. Thesis, Limoges, 2018. http://www.theses.fr/2018LIMO0077/document.
Der volle Inhalt der QuelleUnderstanding the biological mechanisms of action of membrane proteins requires the comprehension of the interactions of xenobiotics with these proteins and with lipid membranes. Experimental methods are often demanding and only partially respond to xenobiotic-membrane-protein interactions. In silico molecular modeling is a serious alternative to tackle these issues. Molecular dynamics (MD) and biased dynamics simulations have opened many perspectives by providing an atomistic description of these intermolecular interactions. Using MD simulations, we built a model of the human ABC ABCC4/MRP4 transporter. We explored the influence of cholesterol on this protein as well as the impact of a polymorphism known to shut down the transport activity of this protein. We also studied the interaction of xenobiotics with this human transporter. The transport cycle of the ABC transporters was investigated in an attempt to better understand how it works.Interactions between lipid membranes and xenobiotics were explored by examining their ability to incorporate lipid membranes. Lipid mixtures with cholesterol showed a significant impact on the human protein ABCC4/MRP4 and on the xenobiotics studied. The importance of regions, domains constituting the ABCC4/MRP4 protein as well as the importance of specific residues has been clearly demonstrated. We also observed intermediates in the transport cycle of an ABC transporter in conjunction with structural changes occurring during this cycle
Basante-Bedoya, Miguel Angel. „Transporteurs lipidiques dans la morphogenèse du champignon pathogène opportuniste de l’Homme Candida albicans“. Electronic Thesis or Diss., Université Côte d'Azur, 2021. http://theses.univ-cotedazur.fr/2021COAZ6030.
Der volle Inhalt der QuelleCandida albicans is a human opportunistic fungal pathogen that can cause superficial or systemic infections; its ability to change from an ovoid to a filamentous form is associated with its virulence. During this highly polarized filamentous growth, an accumulation of vesicles (Spitzenkörper), characteristic of filamentous fungi, as well as a polarized distribution of lipids, such as ergosterol, phosphorylated derivatives of phosphatidylinositol (PI(4)P, PI(4,5)P2) and phosphatidylserine (PS) is observed at the apex of filaments. However, the importance of the asymmetry of these lipids in the membrane bilayer is not completely understood. Flippases (P4-ATPases) transport lipids across the membrane bilayer to generate and maintain its asymmetry. C. albicans has 5 flippases, including Drs2 which is critical for filamentous growth and phosphatidylserine (PS) distribution. Furthermore, a drs2 deletion mutant is hypersensitive to fluconazole and copper. We show here that such a mutant is also critical to virulence in a mouse model of systemic infection. To clarify the role of Drs2 during C. albicans filamentous growth, we studied the distribution of this ATPase, as well as that of key lipids and regulators, during the initiation and maintenance of this growth process. We also characterized point mutants of Drs2, analogous to those altered for PS transport in S. cerevisiae. In addition, we examined the importance of other flippases, such as Dnf1-3, in invasive growth and the role of lipid transporters belonging to the oxysterol binding protein (Osh) family. Our results indicate in particular that Drs2 plays a unique role in the maintenance of invasive filamentous growth of C. albicans, which appears to be more critical after the first septum formation, and that an interaction between Drs2 and Osh4, via PI(4)P, plays an essential role during invasive filamentous growth
Lacabanne, Denis. „Solid-state NMR studies of the ABC transporter BmrA in its lipid environment“. Thesis, Lyon, 2017. http://www.theses.fr/2017LYSE1243/document.
Der volle Inhalt der QuelleATP binding cassette (ABC) transporters can translocate a variety of molecules by coupling drug/lipid efflux with an ATP-Mg2+ fuelled engine. They are found in all forms of life and they are involved in a number of drug resistances including anti-cancer drugs and antibiotics. My studies focus on the drug exporter BmrA (130 kDa) from Bacillus subtilis as a model system and homologue of the human P-glycoprotein that is involved in multidrug resistance in cancer. We show that the reconstitution of this protein in lipids from Bacillus subtilis at a lipid-protein ratio of 0.5 m/m allows an optimal protein insertion into lipid bilayer as well as it complies with the two central NMR requirements: high signal-to-noise in the spectra and sample stability over a time period of years. The obtained spectra point to a well-folded protein and a highly homogenous preparation, as witnessed by the narrow resonance lines and the signal dispersion typical of the expected secondary structure distribution of the membrane protein. In the same time, we adapted the GRecon method used in electron microscopy studies for membrane protein reconstitution to the needs of solid-state NMR sample preparation. We followed in detail the reconstitution of the ABC transporter BmrA by dialysis as a reference, and established optimal reconstitution conditions using the combined sucrose/cyclodextrin/lipid gradient characterizing GRecon. NMR spectra recorded on a sample produced by GRecon showed a highly similar fingerprint as those recorded previously on samples reconstituted by dialysis. GRecon sample preparation presents a gain in time of nearly an order of magnitude for reconstitution. In order to study the inward-facing (IF) and the outward-facing (OF) state of the transporter, we developed a reproducible and quantitative protocol of ATP:Mg2+:VO43- addition inducing the OF state. We used selectively labelled samples obtained by the addition of natural abundance residues in the bacterial medium in order to reduce the number of signals in the spectra of this large protein. We recorded solid-state NMR two-dimensional spectra with different mixing times (20 and 200 ms) in order to follow chemical shift changes and identify residues by sequential correlations. The very noticeable apparition of new signals concomitant with the large amplitude of chemical shift perturbations (CSPs) highlight the important flexibility and conformational changes of the protein in presence of ATP:Mg2+:VO43- substrate. In order to identify the residues appearing in the spectra, we use paramagnetic replacement by Mn2+ of the Mg2+ acting as a co-factor in the active site. The paramagnetic relaxation enhancements caused the Mn2+ revealed that the amino acids appearing in the spectra are located in proximity to the ATP binding pocket. Besides, EPR measurements confirmed the closed state of the protein by identifying the corresponding 1.8 nm distances between two Mn2+. We investigate on the conformational differences identified between the IF and OF state in the ABC transporter BmrA reconstituted in its natural lipids. The observation of numerous CSPs, as well as the apparition new signals are observed for a hydrolysis-incompetent mutant on addition of ATP, indicating that hydrolysis is not required for the IF to OF transition in BmrA. We also analyze the mechanistic of the X-loop motif described to be involved in the communication between two domains of the protein. We observe for a mutant protein in which transport is abolished, but which remains ATPase active, an incomplete transition since only a subset of CSPs is observed, as well as lack of rigidification. This suggests that the change in dynamics might be central for transmitting the relevant conformational changes to the part of the protein driving transport, concomitant of an engine which is turning an input shaft, but which fails to connect in a rigid manner, trough adequate gears, with the output shaft driving the pump
Mathey, Aline. „Nouvelles stratégies thérapeutiques et chimiorésistance : molécules bioactives et métabolisme lipidique“. Electronic Thesis or Diss., Bourgogne Franche-Comté, 2023. http://www.theses.fr/2023UBFCI014.
Der volle Inhalt der QuelleMany therapeutic failures persist due to adaptation and tumor resistance mechanisms, such as insensitivity to cell death signals, the overexpression of drug efflux transporters (i.e. ABC transporters involved in the multidrug resistance phenotype or MDR), mutations in DNA damage detection and repair pathways or reprogramming of energy metabolism. More specifically, an increasing number of studies suggest that deregulations of mitochondrial lipid metabolism, cardiolipins, play a role in tumor progression and aggressiveness, thereby representing an attractive therapeutic target in recent years. As a result, new innovative therapeutic protocols based on the use of bioactive molecules of low toxicity have appeared in order to overcome chemoresistance, reduce toxicity, side effects and potentiate the effectiveness of the chemotherapeutic drug in order to extend the life expectancy and enhance the quality of life of patients. Concerning the first part of this project, we demonstrated for the first time the ability of xanthohumol, a prenylated flavonoid extracted from hops, to restore the induction of DNA damage in colorectal cancer cells and to sensitize the latter to a commonly used clinically anticancer agent, SN38. We have also shown the ability of two essential oils extracted from Apiaceae in Tunisia, Pituranthos chloranthus and Teucrium ramosissimum, to restore the sensitivity of uterine sarcoma cells presenting the MDR phenotype, in particular to doxorubicin, mediated by the induction of apoptosis, the decrease in the overexpression and activity of the ABC transporter P-gp. The work resulting from the second part of this project provided a deeper insight into the existing relationships between cardiolipin metabolism and chemoresistance thanks to the identification of alterations in content, composition of cardiolipins and key molecular factors which represent new potential therapeutic targets in order to restore the sensitivity of tumors to chemotherapies
Azouaoui, Hassina. „Étude structurale et fonctionnelle d’un transporteur de lipides « une flippase » de la levure S. cerevisiae : l’ATPase P4 Drs2p et sa sous unité-associée Cdc50p“. Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS224/document.
Der volle Inhalt der QuelleMaintenance of phospholipid asymmetry in eukaryotic cell membranes is essential for cellular integrity and function. P4-ATPases, from the P-type ATPases family, are energy-dependent transporters, together with their CDC50 accessory subunits couple ATP hydrolysis to lipid transport from the exoplasmic to cytoplasmic leaflet to maintain membrane asymmetry.Drs2p is one of these P4-ATPases in the yeast Saccharomyces cerevisiae. Drs2p is localised in trans-Golgi (TGN) membranes in association with its binding partner Cdc50p, which contributes to the correct addressing of Drs2p and probably in the catalyzed transport by Drs2p. Drs2p transport principally phosphatidylserine (PS) in TGN membranes. The PS is important for a several signalling pathways, for example, in apoptosis and recruitment of the proteins implied in various essential cellular process, so, it's very important to understand the mechanism that establishes this asymmetry.To gain in comprehension of molecular mechanism of lipid transport, robust protocols for expression and purification are required. In this work, we present a procedure for high-yield co-expression of Drs2p and Cdc50p. The purification of Drs2p and Cdc50p is achieved in a single step by affinity chromatography on streptavidin beads, yielding, 1-2 mg purified Drs2p/Cdc50p per liter of culture. This procedure allows purification of the complex Drs2p/Cdc50p with stoichiometry to 1:1. Our complex is functional, overal ATP hydrolysis by the complex is dependent of PS, favourite substrate of Drs2p. This hydrolyze is critically dependent on the presence of PI4P, a phosphoinositide involved in regulation of membrane trafficking.Like many P-type ATPases auto-regulate their activity, we examined the possibility that P4-ATPases are auto-regulated. In this work, we use directed mutagenesis and limited proteolysis associated with mass spectrometry for identify peptides. We show that limited proteolysis of a purified complex Drs2p/Cdc50p resulted in up to a 30-50 fold increase of it ATPase activity, which however remained dependent on PI4P. Using thrombin as the protease, Cdc50p remained intact and in complex with Drs2p, which was cleaved at two positions, namely after R104 and after R1290. Our results therefore reveal that trimming off appropriate regions of the terminal extensions of Drs2p can increase its ATPase activity in the presence of PI4P by an enormous factor, thereby identifying a role of N and/or C-terminal extensions in auto-inhibition of Drs2p.Our results open perspectives on the structural and the functional characterization of the lipid transport mechanism by the complex Drs2p/Cdc50p. Furthermore, our procedures open up the possibility of studying the molecular bases of the pathologies associated with the mutations of human P4-ATPases
Wang, Yuhuan. „ROLES OF ABCG5 ABCG8 CHOLESTEROL TRANSPORTER IN LIPID HOMEOSTASIS“. UKnowledge, 2015. http://uknowledge.uky.edu/pharmacy_etds/50.
Der volle Inhalt der QuelleMcIlwain, Benjamin Carl. „Pharmacology and Lipid Sensitivity of the Prokaryotic Aspartate Transporter, GltPh“. Thesis, The University of Sydney, 2016. http://hdl.handle.net/2123/15002.
Der volle Inhalt der QuelleMostyn, Shannon. „HEADS OR TAILS: LIPID INHIBITORS OF THE GLYCINE TRANSPORTER, GLYT2“. Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/18939.
Der volle Inhalt der QuelleTaylor, Andrew Mark. „Biophysical studies on the human erythrocyte anion transporter, band 3“. Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360571.
Der volle Inhalt der QuelleKrupski-Romsicki, Yolanda. „Modulation of the function of the P-glycoprotein multidrug transporter by lipid environment“. Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0001/NQ43271.pdf.
Der volle Inhalt der QuelleQuazi, Faraz. „The role of photoreceptor ABC transporter ABCA4 in retinal and lipid transport and Stargardt macular degeneration“. Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/45626.
Der volle Inhalt der QuelleButchbach, Matthew E. R. „Regulation of glutamate transport by GTRAP3-18 and by lipid rafts“. Connect to this title online, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1054650123.
Der volle Inhalt der QuelleTitle from first page of PDF file. Document formatted into pages; contains xviii, 160 p.; also includes graphics Includes bibliographical references (p. 132-160). Available online via OhioLINK's ETD Center
Sasaki, Mayumi. „Cloning of ABCA17, a novel rodent sperm-specific ABC (ATP-binding cassette) transporter that regulates intracellular lipid metabolism“. Kyoto University, 2007. http://hdl.handle.net/2433/135646.
Der volle Inhalt der QuelleSands, Eric R. „Cloning and Expression of Thermophilic, Mesophilic, and Psychrophilic Zn2+ Transporting ATPases“. Digital WPI, 2006. https://digitalcommons.wpi.edu/etd-theses/699.
Der volle Inhalt der QuelleSnider, Shayne. „Choline Transport Links Phospholipid Metabolism and Inflammation in Macrophages“. Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/35715.
Der volle Inhalt der QuelleJohnson, Soraya Sarah. „Control of the protein and lipid content of the plasma membrane by ATP-binding cassette transporter proteins in S. Cerevisiae“. Diss., University of Iowa, 2010. https://ir.uiowa.edu/etd/825.
Der volle Inhalt der QuelleJain, Deepak M. „Effect of corn fibre oil and its constituents on cholesterol metabolism and intestinal sterol transporter gene expression in hamsters“. Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98732.
Der volle Inhalt der QuelleLima, Alex da Silva. „Uso da microscopia eletroquímica de varredura (SECM) no estudo de sistemas micelares e do transporte de espécies químicas através de membranas lipídicas“. Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/46/46136/tde-01102015-084001/.
Der volle Inhalt der QuelleThis thesis shows results on the use of scanning electrochemical microscopy in the study of micellar systems and lipid bilayers. Studies involving micellar systems were performed by using SECM in the substrate-generator/tip-collector mode. In this operation mode a platinum microelectrode was positioned close to a platinum substrate and used to monitor electrogenerated species on this surface. Taking into account the time for the electrogenerated species to diffuse from the substrate to the microelectrode, the diffusion coefficient of the electroactive species and of the micelles can be calculated by applying the Einstein-Smoluchowski equation. As micelles are not electroactive, ferrocene electrogenerated on the substrate and incorporated into the micelles was used as a probe to estimate the diffusion time. The results obtained for tetradecyl trimethyl ammonium bromide (C14TABr) corroborate those reported in the literature, demonstrating the applicability of the proposed methodology in the study of micellar systems. Experiments with micelles obtained from 1-alkyl-3-methylimidazolium, CxMelmCl (x = 10, 12, 14, 16) chloride surfactants were also performed and results showed the effect of the carbon chain in the diffusion coefficient. Experiments involving the permeation of chemical species through lipid bilayers were carried out in two steps. A membrane model (cellophane) was preliminary used in order to investigate the possibility of using SECM as a tool for monitoring the permeation of electroactive species through the membrane. Then, a methodology for obtaining microholes in polystyrene sheets used to form lipid bilayers was presented, as well as details about the design of an electrochemical cell used in the permeation experiments. Experiments involving the use of planar lipid bilayers obtained by the method of Miller prepared using soybean lecithin were performed. These experiments were carried out in order to evaluate the stability and to check the permeation of some substances through the prepared bilayers. Permeation experiments were performed by placing the microelectrode close to the membrane with subsequent amperometric detection of any electroactive species that cross the membrane
Kaniti, Archana. „Etudes du mode d'action antipaludique de nouveaux bis-cations“. Thesis, Montpellier 2, 2010. http://www.theses.fr/2010MON20154.
Der volle Inhalt der QuelleIn this thesis I have attempted to subject the issues of mode of action of recently synthesized bis cationic compounds and their possible interactions with chloroquine resistance. Antimalarial activities of representatives of various bis quarternary ammonium compounds, alkyl amidines (received from Dr.Vial group, Montpellier) and of bisbenzyl amidines (received from Chemistry group, Liverpool) activity have been investigated with chloroquine and pentamidine and looked for cross resistance with chloroquine. For this purpose two genetically modified allelically exchanged cell lines C3Dd2 and C2GCO3 modified on the chloroquine resistance-related PfCRT (P.falciparum chloroquine Resistance Transporter) gene were used. Among the benzyl amidines, a significant hypersensitivity tobis benzyl amidines was observed among the isolates bearing the mutant PfCRT. No such difference is observed for the bisalkyl amidines. To understand the mode of action and role of PfCRT, competitive binding assay to heme (which may mediate the well-known cellular accumulation of the compounds) and effect on heme crystallization assays (which is involved in the toxic effect against the intracellular parasite) were performed. All these compounds were shown to interact with heme in various degrees. Their activity was observed not to be correlating with heme crystallization inhibition. This is likely due to the structural differences between the compound which discriminate the compounds in the transport of the compound to the parasite and their mechanism of antimalarial activities. In addition I have studied the effect of pH on the pharmacological activity of the drugs using allelically exchanged genetically modified cell lines (for PfCRT) to characterize the importance of proton gradient on the transport of chloroquine and pentamidine to the intracellular parasite. Significant difference (reduced antimalarial activity with increased pH) in the activity of chloroquine was observed for both the strains. Despite of the high pKa values for pentamidine, there was significant difference in the sensitivity of the strains to this compound, when the pH is changed. As both the diamidines and choline analogs require transporters to cross the membrane barriers and enter the parasite where they accumulate I have also performed initial studies on the molecular characterization of a potential carrier in P.falciparum. Using basic bioinformatic tools, a gene encoding a P.falciparum protein with significant similarity to higher eukaryotes choline transporter was identified and preliminary work for its functional analysis was performed. In conclusion, this work establishes substantial differences between the various classes of bis-cationic compounds essentially (based on benzamidine and choline-analogs alkylkamidine series) concerning their interaction with the infected erythrocyte and their antimalarial activity. The series are diffentallly affected by the PfCRT mutation and the chloroquine resistance. Results suggest that it may be possible to use novel bisbenzyl amidines to specifically target quinoline resistant Plasmodium falciparum malaria, harbouring mutant pfcrt alleles. Taking this idea further and since both classes of compound target the same non-parasite target (heme), it may even be possible to rationally design a quinoline / diamidine drug combination, in which isolates resistant to one partner drug become more sensitive to the other partner, thus delaying the onset of resistance
Li, Hao. „In vitro Studies of Genodermatoses Affecting Cytoskeletal Integrity and Lipid Processing in Human Epidermis : Pathogenic Mechanisms and Effects of Retinoid Therapy“. Doctoral thesis, Uppsala universitet, Institutionen för medicinska vetenskaper, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-172863.
Der volle Inhalt der QuelleRodrigues, Alice Cristina. „Efeito da atorvastatina sobre a atividade funcional e expressão de transportadores de membrana do tipo ABC e SLC“. Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-19052009-200620/.
Der volle Inhalt der QuelleSpecific membrane transporters have a significant impact on drug absorption and disposition. Most of them belong to two super-families, ABC (ATP-binding cassette) and SLC (solute-linked carrier). Statins are important therapeutic agents in the management of hypercholesterolemia, and considerable inter-individual variation exists in response to its therapy. The effects of atorvastatin expression of efflux (ABCG2 and ABCC2) and uptake (SLCO1B1, SLCO2B1 and SLC22A1) drug transporters were investigated by qPCR in Caco-2 and HepG2 cell lines and in peripheral blood mononuclear cells (PBMCs) of eighteen normolipidemic (NL) and twenty two hypercholesterolemic (HC) individuals treated with atorvastatin (10mg/day/4 weeks). The possible involvement of ABCB1 C3435T polymorphism in ABCB1 mRNA expression was also evaluated. In vitro studies with the cell lines HepG2 and Caco-2 were also performed. The effect of atorvastatin on the activation of the promoter of ABCB1 by transcription factors (NF-kappaB, NF-Y, c-jun, SP-1, and PXR) was evaluated by electrophoretic mobility shift assay (EMSA), and ABCB1 mRNA half-life were measured by PCRq. The expression and functional activity of ABCB1 were investigated by Western blot, imunohistochemistry and flow cytometry. Immunohystochemical analysis revealed that ABCB1 is located at the apical membrane of the bile canaliculi in HepG2, and in apical membrane of Caco-2 cells. Atorvastatin treatment of HepG2 cells caused a decreased in ABCB1 and an increase in ABCC2 and ABCG2 transcript levels. These effects were time and dose-dependent. Treatment of Caco-2 cells did not present any differences in efflux transporters mRNA levels. Treatment of HepG2 cells with 10 and 20 M atorvastatin caused a reduction on ABCB1 expression (0 µM: 1,00 ± 0,06; 10 µM: 0,69 ± 0,25, p< 0,05; 20 µM: 0,69 ± 0,06, p< 0,05), and a 41% decrease in ABCB1-mediated efflux of Rhodamine123 (p < 0.01). Although reduced ABCB1 mRNA expression was not due to any repressor protein suppressing ABCB1 promoter activation, mRNA stability studies revealed that mRNA stability of ABCB1 was markedly decreased by atorvastatin treatment (2h versus 7h for control). In agrrement with these results, in PBMCs of HC individuals, atorvastatin treatment also reduced ABCB1 mRNA expression. However, the down-regulation was not associated with the presence of 3435T allele. For the uptake transporters, atorvastatin decreased SLC22A1 transcript levels after 30min-treatment and it was not regulated in HepG2. On the other hand, SLCO2B1 was up-regulated after 24h-treatment of HepG2 cells. In vivo studies with PBMCs revealed that during hypercholesterolemia all the drug transporters analyzed were increased almost 10-fold (p< 0.05), and after atorvastatin therapy the efflux and uptake transporters transcript levels were all down-regulated. These findings suggest that atorvastatin exhibits differential effects on mRNA expression of drug transporters depending on the cell type, which may be related to tissue-specific expression of transcription factors. Atorvastatin leads to decreased ABCB1 function and synthesis in HepG2 cells by increasing degradation of ABCB1 mRNA. Therefore, inhibition of ABCB1 may reduce atorvastatin elimination via bile, increasing its cellular concentrations. We also may suggest that in PBMCs cholesterol modulates mRNA expression of drug transporters, and this may contribute to the variability of response to atorvastatin.
Al-Khfajy, Wrood Salim Dawood. „Role Of Transmembrane 141 in Cholesterol Metabolism“. Kent State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=kent1416142859.
Der volle Inhalt der QuelleFlinois, Thomas. „Modification d'électrodes par des films redox-actifs, des lipides et des transporteurs ioniques membranaires : vers l'élaboration d'une pile biomimétique“. Thesis, Rennes 1, 2019. http://www.theses.fr/2019REN1S093.
Der volle Inhalt der QuelleBased on the transmembrane ion transport processes of living cells, the design of a biomimetic fuel cell can be considered. Its principle relies on ion or proton concentration gradients induced by the protein NhaA, a transmembrane Na+/2H+ antiport, to generate electrical energy. This thesis contributes to the development of this device through electrode modifications to detect the activity of ionic transporters at the electrode/biomimetic membrane interface.A bibliographic review of the fundamental aspects of cell membranes and of the biomimetic fuel cell principle is presented. Electrodes modified by electrodeposition of salicylic acid derivatives have yielded redox-active films sensitive to pH changes or monovalent and monoatomic ions concentration. The stability of the lipid deposit onto the electrodes was significantly increased by the electrografting of 4-decylaniline. This anchored and stable lipid deposit makes it possible to obtain biomimetic membranes allowing the insertion of ionic transporters. The activity of the ion carriers inserted into the biomimetic membranes has been monitored through the redox-active films' potential that is dependent on pH or on sodium or potassium ions concentrations at the electrode/membrane interface
Hakizimana, Pierre. „Phosphatidylethanolamine regulates the function and the structure of LmrP, a bacterial multidrug transporter protein associated to antibiotic resistance“. Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210486.
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Doctorat en Sciences
info:eu-repo/semantics/nonPublished
Freire, Camilla Camerino Santana Davino. „Metabolismo de lipídeos em inseto coleóptero: digestão e transporte de ácidos graxos“. Universidade Federal de Alagoas, 2018. http://www.repositorio.ufal.br/handle/riufal/3421.
Der volle Inhalt der QuelleFAPEAL - Fundação de Amparo à Pesquisa do Estado de Alagoas
Os coleópteros constituem uma ordem de insetos bastante conhecidos como besouros. A maioria das espécies de coleóptero são insetos fitófagos e por esta razão constituem importantes pragas de culturas e de armazenamento, como o Tribolium castaneum. O metabolismo de lipídeos é importante para as funções biológicas de insetos, exercendo papel na geração de energia metabólica e em outros processos celulares. As proteínas transportadoras de ácidos graxos (FATPs) exercem papel crucial no transporte de ácidos graxos extracelulares para as células, possuem sequência conservada entre as espécies e estão envolvidas na síntese de hormônios e feromônios. Estudos recentes mostram que o silenciamento do gene para FATPs através de técnicas de RNA de interferência (RNAi) em insetos afetam a absorção de ácidos graxos e a síntese de feromônio. Este trabalho tem como objetivo caracterizar proteínas homólogas à FATPs presentes no genoma de Tribolium castaneum, avaliar a expressão gênica nos tecidos, fases de desenvolvimento e em insetos tratados com Orlistate e avaliar o efeito do silenciamento de FATPs no metabolismo energético. Foram realizadas análises bioinformáticas com as sequências de aminoácidos e a avaliação da expressão gênica foi realizada por PCR em tempo real. Os efeitos do fármaco Orlistate foram avaliados através de qPCR e análise dos índices nutricionais. A busca de sequências no genoma do T. castaneum revelou duas sequências de proteínas homólogas à FATPs e a análise bioinformática foi realizada. O estudo da expressão gênica de FATPs por qPCR demonstrou maior expressão dos dois genes no corpo gorduroso de larvas e expressão considerável em todos os estágios de desenvolvimento do inseto, com maior expressão no estágio de pupa. Os efeitos do Orlistate na expressão das FATPs evidenciaram a influência da composição da dieta na regulação da expressão gênica dessas proteínas. O silenciamento gênico de TcasFATP foi alcançado, mas não foram observados efeitos diretos na dinâmica energética das larvas, pois os níveis de triacilglicerol e as taxas de β-oxidação não foram afetadas. Dessa forma, estudos mais detalhados com uso do silenciamento gênico serão necessários para melhor caracterização funcional das FATPs e elucidação do seu papel no metabolismo energético do inseto.
Ohlwein, Nina. „Endocytosis controlled by monolayer area asymmetry“. Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2011. http://dx.doi.org/10.18452/16403.
Der volle Inhalt der QuelleEndocytic engulfment requires high local membrane curvature and causes significant area changes of the membrane leaflets. This can be initiated by differences between the surface areas of the two monolayers related to leaflet specific modulation of lipid composition. Thus, it was proposed that lipid translocators, pumping phospholipids from the outer to the inner leaflet, account for monolayer area asymmetry as an early step in endocytosis. To elucidate the influence of this asymmetry on endocytosis, surface area relation was altered by adding exogenous phospholipids to living cells and changes in endocytic activity were quantified. Depending on the lipid species, exogenous lipids were only incorporated into the outer layer or subsequently translocated across the plasma membrane thereby increasing either the outer or inner surface area. Addition of different analogues of aminophospholipids, which are translocated to the inner leaflet, led to an enhancement of bulk flow endocytosis in K562 cells. Moreover, our data indicate that clathrin-mediated endocytosis of Hep2 cells was stimulated as well. Inversely, addition of phospholipids, which remain on the outer layer, reduced bulk flow or clathrin-mediated endocytosis in various cell lines. Notably, also clathrin-mediated endocytosis was influenced by the addition of lipids, although many proteins noted for their ability to induce membrane curvature are known to be implicated in this pathway. This corroborates a recent model how aminophospholipid translocases are implicated in endocytosis. Upon translocating lipids and additionally interacting with endocytic accessory proteins, lipid translocators could integrate two processes to generate curvature: membrane bending based on monolayer area asymmetry and protein-related mechanisms. Collectively, findings in the present study suggest that curvature generation in endocytosis is supported by the induction of monolayer area asymmetry mediated by the translocation of lipids.
Karlsson, Emma. „Compositional clues to sources and sinks of terrestrial organic matter transported to the Eurasian Arctic shelf“. Doctoral thesis, Stockholms universitet, Institutionen för miljövetenskap och analytisk kemi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-116876.
Der volle Inhalt der QuelleAt the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.
Jacquot, Aurore. „Co-expression et caractérisation fonctionnelle d’un transporteur de lipides (une « flippase ») de la levure S. cerevisiae : l’ATPase P4 Drs2p, en complexe avec sa sous-unité associée Cdc50p“. Thesis, Paris 11, 2012. http://www.theses.fr/2012PA11T081/document.
Der volle Inhalt der QuelleTrans-Golgi membranes and plasma membranes of eukaryotic cells are asymmetric, with their cytosolic leaflet enriched in aminophospholipids (APLs: phosphatidylserine and phosphatidylethanolamine). Dissipation of this asymmetry is involved in many (patho)physiological processes. P4 ATPases are prime candidates for APL transport and for maintaining asymmetry across membranes. In addition, yeast deleted for P4 ATPases display membrane trafficking defects. Besides, CDC50 proteins have been shown to interact physically with P4 type ATPases, and this interaction is important for addressing the complex to the right destination, and possibly also for its function. To gain insight into the molecular mechanism of lipid transport by P4 ATPases, the goal of my thesis was to develop the co-expression, in yeast, of a functional P4 ATPase, Drs2p, together with its partner, Cdc50p. The strategy we developed allowed us to obtain a membrane fraction enriched in Drs2p (~3%), mainly in complex with Cdc50p. Functional characterization of the complex identified phosphatidylinositol-4-phosphate (PI4P), a major regulator of membrane trafficking, as a crucial component for rapid completion of the Drs2p/Cdc50p catalytic cycle. We also purified the complex in one step on streptavidin beads. Finally, we started investigating the potential auto-inhibitory roles of the C-terminus (as the C-terminus of Drs2p contains a PI4P binding site) and the N-terminus of Drs2p, by expressing various truncated versions of Drs2p. Our work sets the stage for detailed functional and structural characterization of the Drs2p/Cdc50p complex and its role in membrane traffic
Trotier-Faurion, Alexandra. „Optimisation pharmacologique des dérivés de la créatine pour le traitement du déficit en transporteur de la créatine“. Phd thesis, Université Paris Sud - Paris XI, 2013. http://tel.archives-ouvertes.fr/tel-00806976.
Der volle Inhalt der QuelleCarswell, Casey. „The Structural Characterization of Two Prokaryotic Membrane Proteins: CfrA and ELIC“. Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31214.
Der volle Inhalt der QuelleHardy, Lise. „Identification de nouveaux acteurs du métabolisme des HDL : impact sur les maladies cardiovasculaires Critical role of the human ATP-binding cassette G1 transporter in cardiometabolic diseases A Genome Wide Association Study on plasma FV levels identified PLXDC2 as a new modifier of the coagulation process“. Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS546.
Der volle Inhalt der QuelleSince low concentrations of High-Density Lipoproteins-cholesterol (HDL-C) are associated with increased cardiovascular disease (CVD) risk, HDL are recognized as protective in atherosclerotic CVD (ASCVD). Indeed, HDL promote lipid efflux from macrophages and other atheroprotective activities. Here, we aimed to identify new factors implicated in the determination of atheroprotective functions of HDL. ATP-Binding Cassette G1 (ABCG1) transporter perform cholesterol, phospholipids or vitamin efflux from peripheral macrophages to HDL. We showed that ABCG1 expression in hepatocytes promoted HDL phospholipid content rearrangement. This HDL remodeling is associated with a better cholesterol efflux capacity and an improvement of their anti-inflammatory properties. Simultaneously, epidemiological studies allow us to identify a novel transcription factor, ZNF471 (Zinc Finger Protein 471). ZNF471 seems to modulate expression and activity of key proteins implicated in lipid metabolism, through epigenetic DNA methylation regulation. We highlighted that ZNF471 expression in hepatocytes increased DNA methylation in CETP (Cholesterol Ester Transfer Protein) gene promoter region. As a consequence, CETP gene expression and protein activity were diminished, which raised HDL-C circulating concentrations. We also pointed out that ZNF471 expression stimulated HDL cholesterol efflux capacities. This work allows the identification of novels genetic and epigenetic actors in determining HDL lipoproteins activities. It paves the way for new therapeutic and mechanistic insights on the roles of HDL in ASCVD
Gumí, Audenis Berta. „Structural organization of model membranes: a complementary approach combining atomic force microscopy and X-ray techniques“. Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/550973.
Der volle Inhalt der QuelleLes membranes biològiques (BMs) són fronteres autosegellants, que limiten les barreres permeables de les cèl·lules i els orgànuls i proporcionen els mitjans necessaris per compartir funcions. A part de ser crucials per l’estructura cel·lular, proporcionen una matriu de suport per a totes les proteïnes que es troben inserides a la cèl·lula, actuant com canals per l’intercanvi de massa, energia i informació amb l’exterior. Les BMs intervenen en moltes funcions biològiques, com el tràfic, la divisió cel·lular, l’endocitosi i l’exocitosi, que exigeixen canvis conformacionals durs en la membrana lipídica com la fusió, la fissió o el creixement de tubs. La correlació entre la composició i l’empaquetament dels lípid regeix les propietats fisicoquímiques de la membrana i la seva estructura mecànica Considerant la complexa diversitat química de les BMs, sistemes de membranes model són utilitzats sovint per estudiar propietats de membrana. Degut a la heterogeneïtat de les BMs i la conseqüent necessitat de tècniques locals per a explorar BMs a escala nanomètrica, sistemes de bicapes suportades, com les bicapes de lípids suportades (SLBs), s’han proposat com models, ja que conserven l’ordre bidimensional i la mobilitat lateral, oferint ambients excel·lents per a la inserció de proteïnes de membrana. Diversos informes demostren la gran varietat de tècniques útils per estudiar membranes lipídiques suportades i sense suport. Gràcies a la possibilitat de treballar sota un ambient controlat i amb una resolució nanomètrica en distància i força, la microscòpia de forces atòmiques (AFM) és, avui en dia, una tècnica ben establerta tant per a obtenir una imatge de la morfologia com per mesurar les propietats locals físiques i mecàniques de les SLBs mitjançant modes d’espectroscòpia de forces (AFM-FS). De totes formes, la resolució que s’obté amb l’AFM és inferior a la que es pot obtenir amb tècniques de raigs X (XR) i neutrons. L’objectiu general d’aquesta tesis és investigar les propietats fisicoquímiques i estructurals de membranes lipídiques model combinant tècniques d’AFM, d’AFM-FS i de XR. També proposem metodologies avançades basades en AFM-FS i XR, així com l’acoblament de les dues tècniques per dur a terme experiments locals in situ. A més, amb AFM i AFM-FS també hem caracteritzat sistemes vesiculars que no contenen fosfolípids, els quals tenen una aplicació tecnològica: actuar com a nanotransportadors per al lliurament de fàrmacs.
Brown, Dustin Paul. „TARGET-DIRECTED BIOSYNTHETIC EVOLUTION: REDIRECTING PLANT EVOLUTION TO GENOMICALLY OPTIMIZE A PLANT’S PHARMACOLOGICAL PROFILE“. UKnowledge, 2015. http://uknowledge.uky.edu/neurobio_etds/13.
Der volle Inhalt der QuelleSigrüner, Alexander [Verfasser]. „ABCA transporters and associated genes in lipid metabolism / vorgelegt von Alexander Sigrüner“. 2007. http://d-nb.info/986961256/34.
Der volle Inhalt der QuelleHsiao, Man-Yun, und 蕭蔓妘. „Extraction of membrane lipid rafts from gills of euryhaline fish and salinity effects on abundance of ion transporters in branchial lipid rafts“. Thesis, 2018. http://ndltd.ncl.edu.tw/handle/bfwwyh.
Der volle Inhalt der Quelle國立中興大學
生命科學系所
106
Lipid rafts are microdomains of the plasma membrane enriched in cholesterol, sphingolipids, glycosphingolipids and proteins (e.g. Flotillin). Lipids in the lipid raft are composed of long-chain saturated fatty acids, which make it insoluble in nonionic detergents. In previous studies on mammalian cells, ion exchanges mainly occurred in lipid rafts. However, in fish, there are few studies on lipid rafts. Therefore, the aim of the present study is to establish the extraction method of lipid rafts in fish gills, and to investigate the localization and protein expression of the ion transporters in the lipid rafts of fish gills. In the first part of this study, the amino acid sequence of the Na+, K+-ATPase (NKA) was predicted to possess more N-Myristoylation and Palmitoylation sites than that of the vacuolar-type H+-ATPase (V-HA). Thus, the NKA might have a higher tendency to locate on lipid rafts, compared to the V-HA. Salinity effects on distribution of NKA and Flotillin were found in lipid rafts of medaka gills, but the relations between NKA and Flotillin were not clear yet. Meanwhile, 0.1% Triton X-100 and 0.05% Tween 20 were found to successfully extract lipid rafts from milkfish and tilapia gills, respectively. In the second part of this study, the distribution of NKA was found only in lipid rafts of milkfish and tilapia gills, and distribution of NKA in the freshwater (FW) group was significantly higher than the seawater (SW) group. However, expression of NKA was not affected by lipid raft contents. On the other hand, V-HA isoform1 and isoform2 of milkfish gills as well as V-HA of tilapia gills appeared in the lipid rafts and non-lipid rafts of cell membrane. Distribution of V-HA isoform1 and isoform2 in non-lipid rafts was significantly higher of the FW milkfish gills than the SW group. Most V-HA distribution was found in non-lipid rafts of tilapia gills, significantly higher in the FW group than the SW group. In summary, this study has established the extraction method of lipid rafts on milkfish and tilapia gills. The NKA of milkfish and tilapia gills was located only in lipid rafts of cell membrane, and its expression was not affected by contents of the lipid rafts. V-HA was mainly localized in non-lipid rafts of both milkfish and tilapia gills with significant differences in expression between the SW and FW groups.
Gulati, Sonia. „Characterizing the Interaction of the ATP Binding Cassette Transporters (G subfamily) with the Intracellular Protein Lipid Environment“. Thesis, 2011. https://doi.org/10.7916/D8ZW1SW7.
Der volle Inhalt der QuelleTan, Kah Poh. „Nuclear Factor (Erythroid 2-like) Factor 2 (Nrf2) as Cellular Protector in Bile Acid and Retinoid Toxicities“. Thesis, 2008. http://hdl.handle.net/1807/17287.
Der volle Inhalt der QuelleMendes, Maria Manuel Feliciano da Costa. „Lipid nanoparticles as a versatile system for drug administration“. Master's thesis, 2016. http://hdl.handle.net/10316/36494.
Der volle Inhalt der QuelleA nanotecnologia é uma ciência emergente com aplicação em diferentes áreas, com especial ênfase nas ciências da saúde. As nanopartículas de lipídicas (NL) são um nanosistema promissor para a entrega de fármacos, que suscita interesse particular em comparação com os sistemas coloidais convencionais. A sua natureza biocompatível e biodegradável, a estabilidade físico-química, o controle sobre a libertação do fármaco, relação custo-eficácia e fácil transposição de escala são algumas das suas vantagens. As NL tem sido avaliadas para administração por várias vias, superando, assim, algumas limitações associadas às formas farmacêuticas de dosagem convencionais. Neste trabalho, o objetivo principal foi o desenvolvimento e caracterização de formulações orais e transdérmica baseadas em nanopartículas lipídicas para co-encapsulação de olanzapina (OL) e de sinvastatina (SV). A aplicação particular das NL para administração oral, é vantajosa, devido ao efeito potenciador dos lípidos na absorção do fármaco e a na sua absorção preferencial pelo sistema linfático, evitando o efeito de primeira passagem hepática e assim, aumentar a biodisponibilidade oral. Por sua vez, a sua utilização na administração transdérmica pode aumentar a penetração dos fármacos, como resultado do efeito oclusivo promovido pelo pequeno tamanho das partículas e a pela sua adesividade. Na administração oral, foi realizada uma dupla abordagem de desenvolvimento. Em primeiro lugar, pretendeu-se avaliar a exequibilidade de transposição de escala das nanopartículas lipídicas e, subsequentemente, da conversão de NLC numa forma de dosagem sólida e flexível, em termos de modulação de libertação dos fármacos. Para isso, as dispersões de Combo-NLC foram produzidas por homogeneização a alta pressão, e avaliada em termos de estabilidade, processo de secagem, desempenho dos comprimidos na libertação in vitro e na permeabilidade intestinal. As NLC revestidas com polímeros permitiram obtenção de mecanismos de liberação distintos, incluindo libertação imediata, retardada e prolongada. Os estudos de citotoxicidade e de permeabilidade foram realizados para todas as formulações. A melhor formulação foi associada à baixa toxicidade e alta permeabilidade intestinal, o que pode ainda resultar num melhoramento permeabilidade oral. Tais resultados poderiam ser atribuídos à proteção dos fármacos e controle sobre liberação promovido pela NLC. Na administração transdérmica, como segunda abordagem, um sistema monolítico de fármaco-nas-NLC-no-adesivo foi desenvolvido, formulado e caracterizado por metodologias 10 in vitro, in silico e viabilidade celular. Foram aplicadas estratégias passivas para aumentar a permeação dos fármacos, como as nanopartículas lipídicas juntamente com promotores químicos de permeação, e microagulhas usadas como método activo. Em primeiro lugar, foi avaliada a combinação de NL com diferentes promotores em termos de comportamento de permeação. O propileno glicol revelou o maior valor de permeação para os dois fármacos. Estes resultados foram complementados por estudos de dinâmica molecular. Depois, diferentes adesivos foram formulados e convenientemente avaliados. Entre todos os adesivos testados, a combinação entre PVP K30 e PEG 400 resultou na permeação do fármaco mais elevada através da pele, simultaneamente revelou as melhores propriedades adesivas in vitro-in vivo. A influência do promotor químico de permeação e o adesivo sobre o desempenho formulação foi racionalizada usando um planeamento factorial. Os resultados mostraram que a presença do adesivo é importante para promover a permeação através da pele, enquanto que a permeação de SV é influenciado principalmente pela presença do promotor químico. Finalmente, avaliou-se a influência das micro-agulha. Esta abordagem combinada não demonstrou uma melhoria significativa sobre a permeação dos fármacos, o que pode indicar que a própria formulação proporciona a principal força motriz para a permeação dos fármacos na pele. Os estudos de citotoxicidade revelaram que as nanopartículas de lipídicas são capazes de reduzir a citotoxicidade associada à SV em solução a concentrações inferiores a 90 μM e que o efeito isolado de adesivo em termos de citotoxicidade foi mais elevado do que o induzido pelo promotor químico. Utilizando esta abordagem combinatória, o projecto demonstrou a versatilidade das nanopartículas de lípidos como sistemas para administração de fármacos coloidais.
Nanotechnology is an emerging science with application in different areas, with special emphasis on health sciences. Lipid nanoparticles (LN) are a promising nanosystem for drug delivery, which has raised particular interest in comparison to conventional colloidal systems. Their biocompatible and biodegradable nature, physicochemical stability, control over drug release, cost-effectiveness and easy scaling-up are some of their advantages. LN have been assessed for administration by several routes, thereby overcoming some limitations associated to conventional dosage forms. In this work, the main aim was the development and characterization of oral and transdermal formulations based on lipid nanoparticles for co-delivery of olanzapine (OL) and simvastatin (SV). The particular application of LN for oral administration is advantageous, due to the enhancer effect of lipids on drug absorption and their preferential uptake by the lymphatic system, thus avoiding liver first pass and increasing bioavailability. In turn, their use in the transdermal administration can increase drug penetration, as a result of the occlusive effect promoted by the small particle size and adhesiveness. In oral administration, a dual step development approach was carried out, firstly, focused on the assessment of the NLC scale-up feasibility, and subsequently, on the conversion of NLC into a solid and flexible dosage form, in terms of drug release modulation. For that, Combo-NLC dispersions were produced by high pressure homogenization, and evaluated in terms of scalability, drying procedure, tableting and performance from an in vitro release and permeability perspective. Modified NLC formulations with the polymers allowed to obtain distinct release mechanisms, including immediate, delayed and prolonged release. Cytotoxicity and permeability studies were performed in order to assess all formulations. The better formulation was associated to low cytotoxicity and high intestinal permeability, which can further result in enhanced oral permeability. Such findings could be ascribed to drug protection and control over release promoted by the NLC. In transdermal administration, as second approach, a transdermal drug delivery system based on an innovative drug-in-LN-in-adhesive design and adhesive composition was formulated and characterized by in vitro, in silico and cellular viability methodologies. As enhancement permeation strategies, passive, including LN coupled with chemical penetration enhancers, CPEs, and microneedles as active method were investigated. Firstly, it was assessed the combination of LN with different enhancers in terms of permeation behaviour. 12 Propylene glycol revealed the higher permeation of both drugs. These results were supported by molecular dynamics studies. After that, different adhesives were formulated and suitably evaluated. Among all adhesives tested, the combination between PVP k30 and PEG 400 resulted in the higher drug permeation across the skin, along with the best in vitroin vivo adhesive properties. The influence of the enhancer and the adhesive on the formulation performance was rationalized using a factorial design. Results showed that the presence of adhesive is crucial to promote of permeation through the skin, while permeation of SV is mainly influenced by the presence of enhancer. Finally, the pre-application of a microneedle device followed by the optimal patch was evaluated. This combined approach did not a show a significant improvement over the drug permeation, which may indicate that the formulation itself provides the main driving force for skin permeation. Cytotoxicity studies revealed that lipid nanoparticles are able to reduce cytotoxicity associated to the SV in solution at concentrations lower than 90 !M!! and it can be visualized that the isolated effect of adhesive in terms of cytotoxicity was higher than the one induced by the enhancer. Using this combinational approach, the project demonstrated the versatility of the lipid nanoparticles as colloidal systems for drug administration.
Pandey, Aparamita. „Glucose and Lipid Metabolism during Pregnancy and Lactation in Rats : Role of Undercarboxylated Osteocalcin“. Thesis, 2016. http://etd.iisc.ac.in/handle/2005/3074.
Der volle Inhalt der QuellePandey, Aparamita. „Glucose and Lipid Metabolism during Pregnancy and Lactation in Rats : Role of Undercarboxylated Osteocalcin“. Thesis, 2016. http://hdl.handle.net/2005/3074.
Der volle Inhalt der QuelleChang, Shu-Wen, und 張書聞. „Effects of Collapsing Response Mediator Protein 2 on Glucose Transporter Type 4 Translocation and Lipid Metabolism in Adipocyte Differentiation via Cytoskeleton Dynamics“. Thesis, 2016. http://ndltd.ncl.edu.tw/handle/27002176841105689762.
Der volle Inhalt der Quelle國立陽明大學
醫學生物技術暨檢驗學系
104
Diabetes mellitus is a metabolic abnormality defined by hyperglycemia resulting from defects in insulin action and/or insulin secretion. Diabetic patients with long-term hyperglycemia are susceptible to develop multiple complications and neurodegenerative diseases due to hyperglycemia-resulted oxidative stress and damage. Cytoskeleton is abnormally assembled and neurotransmission is impaired in neurodegenerative diseases. Moreover, alterations in cytoskeleton dynamics have been implicated in insulin action, glucose transporter type 4 (GLUT4) translocation and trafficking of lipid droplets in adipocytes. Collapsin response mediator protein 2 (CRMP2) regulates neurite outgrowth through mediating microtubules dynamics, which is regulated by glycogen synthase kinase-3β (GSK-3β), the important mediator in the signaling of insulin and GLUT4 translocation. Accordingly, we hypothesized that CRMP2 may be involved in energy homeostasis and thus adipocyte differentiation (adipogenesis). The aim of this study is to investigate expression profile and effects of CRMP2 on glucose and lipid metabolism in adipogenic process of 3T3-L1 pre-adipocytes under high (hyperglycemia) or low (normoglycemia) glucose environment. Our results showed that CRMP2 overexpression in mature adipocytes led to reduced lipids accumulation and decreased expression of fatty acid synthesis enzyme (acetyl CoA carboxylase, ACC and fatty acid synthase, FAS) and adipogenesis marker peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein α (C/EBP-α) and fatty acid binding protein 4 (FABP4), while actin filament polymerization is increased. In contrast, knockdown of CRMP2 expression attenuated the above effects. Besides, CRMP2 expression and basal glucose uptake activity were significantly increased in cells under normoglycemic (100 mg/dL) condition. Although lipids contents were reduced in cells exposed to low glucose, expression of PPAR-γ, FABP4 and GLUT4 were elevated. Nevertheless, glucose levels did not affect CRMP2 mRNA levels and proteasomal degradation in adipogenic process. The above results suggest that under physiological glucose environment, the increased CRMP2 expression may result in upregulation of FABP4, PPAR-γ and GLUT4 that facilitates adipocyte differentiation as well as glucose uptake. In addition, the CRMP2-mediated decrease of fatty acid synthesis enzymes and adipogenesis markers and increase of cytoskeleton polymerization result in the reduced lipid accumulation. The above results suggest that CRMP2 may participate in diabetic pathogenesis and diabetic neuropathy through mediating lipid and glucose metabolism in response to external nutrient condition.
Dagenais, Bellefeuille Steve DB. „Nitrate metabolism in the dinoflagellate Lingulodinium polyedrum“. Thèse, 2015. http://hdl.handle.net/1866/15897.
Der volle Inhalt der QuelleDinoflagellates are unicellular eukaryotes found in most aquatic ecosystems of the world. They are major contributors to carbon fixation in the oceans, either as free-living phytoplankton or as symbionts to corals. Dinoflagellates are also infamous because some species can form spectacular blooms called red tides, which can cause serious damage to ecosystems, human health, fisheries and tourism. One of the factors often correlated with algal blooms are increases in nutrients, particularly nitrogen and phosphorus. Nitrate is one of the main components of agricultural runoffs, but also the most abundant bioavailable form of nitrogen in marine environments. Thus, agricultural activities have globally contributed to the magnification of the problems associated with red tides. However, bloom formation and persistence cannot be ascribed to human pollution alone, because other biotic and abiotic factors are at play. Particularly, it is difficult to assess the relative importance of nitrate addition over these other factors, because nitrate metabolism in dinoflagellate is mostly unknown. Filling part of this gap was the main goal of this thesis. I selected Lingulodinium polyedrum as a model for studying nitrate metabolism, because this dinoflagellate can easily be cultured in the lab and a recent transcriptomic survey has provided an almost complete gene catalogue for this species. It is also interesting that some molecular components of the nitrate pathway in this organism have been reported to be under circadian control. Thus, in this project, I used physiological, biochemical, transcriptomic and bioinformatic approaches to enrich our understanding of dinoflagellate nitrate metabolism and to increase our appreciation of the role of the circadian clock in regulating this important primary metabolic pathway. I first studied the particular case of dinoflagellate blooms that occur and persist in conditions of nitrogen depletion. This idea may seems counterintuitive, because nitrogen addition rather than depletion, is generally associated with algal blooms. However, I discovered that when nitrate was added to nitrogen-deficient or nitrogen-sufficient cultures, those that had been acclimated to nitrogen stress were able to survive for about two months at high cell densities, while non-acclimated cells died after two weeks. In conditions of severe nitrogen limitation, cells could survive a little bit more than two weeks by arresting cell division and reducing photosynthetic rates. The incapacity to synthesize new amino acids for these deprived cells in a context of on-going photosynthesis led to the accumulation of reduced carbon in the form of starch granules and lipid bodies. Interestingly, both of these carbon storage compounds were polarized in Lingulodinium cells, suggesting a functional role. The second contribution of my thesis was to identify and characterize the first nitrate transporters in dinoflagellates. I found that in contrast to plants, Lingulodinium had a reduced suite of nitrate transporters and only members of the high-affinity nitrate transporter 2 (NRT2) family were predicted to be functionally relevant in the transport of nitrate. The main transporter was constitutively expressed, which suggested that nitrate uptake in Lingulodinium was mostly a constitutive process rather than an inducible one. I also discovered that nitrate uptake in this organism was light-dependent and not a circadian-regulated process, as previously suggested. Finally, I used RNA-seq to verify if any transcripts involved in the nitrate metabolism of Lingulodinium were under circadian control. Not only did I discovered that there were no daily variations in the level of transcripts involved in nitrate metabolism, but also that there were no changes for any transcripts present in the whole transcriptome of Lingulodinium. This discovery showed that the circadian timer in this species did not require rhythmic transcription to generate biological rhythms, as observed in other eukaryotes.
Mok, Leo. „In Vitro Characterization of the Function of ABCA1: Effects of Naturally Occurring Mutations“. Thesis, 2010. http://hdl.handle.net/1974/5434.
Der volle Inhalt der QuelleThesis (Ph.D, Pathology & Molecular Medicine) -- Queen's University, 2010-02-12 11:14:11.381