Dissertations / Theses on the topic 'Lipid'
To see the other types of publications on this topic, follow the link: Lipid.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Lipid.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Kotland, Vojtěch. "Separace lipidů z buněčných tkání." Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2019. http://www.nusl.cz/ntk/nusl-401857.
Full textAbstract:
This master’s thesis is focused on lipid separation from tissue cells. Thesis is divided into theoretical and experimental part. In the theoretical part is summarized current knowledge about lipids, their properties and methods used to separate them from tissue cells. Those methods were compared and one of them was chosen to be used in the experimental part. Theoretical part is ended with reviews aimed towards the research in this area of chemistry. Experimental part describes factors affecting chosen method of lipid separation from tissue cells. The measurements were chosen so that they could be easily reproduced. Values for each factor were experimentally determined to increase the amount of fat separated. All factors were compared and based on their summarization the optimization for whole method was produced.
2
Dennison, Andrew. "Neutron reflectivity studies of insulin and phosphatidylcholine floating lipid bilayers." Thesis, University of Sheffield, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.574586.
Full text
3
Wood, David. "Lipid Screening and Lipid Disorders in Children." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/etsu-works/7684.
Full text
4
Deeney, Jude T. "Micro lipid droplet precursors of milk lipid globules." Thesis, Virginia Tech, 1985. http://hdl.handle.net/10919/45673.
Full textAbstract:
The lipid in milk (milk fat) is found in the form of droplets
known as milk lipid globules (MLG). These milk lipid globules are
encompassed by a unit membrane known as the milk lipid globule
membrane (MLGM) which is derived from the apical plasma membrane of
the mammary epithelial cell during secretion. In lactating mammary
epithelial cells, immediate precursors of milk lipid globules appear
to be cytoplasmic lipid droplets (CLD). These cytoplasmic lipid
droplets have diameters >1 μm and are characterized by an electron
dense, granular surface coat. A previously unrecognized group of
structures with diameters <.5 μm, which resemble cytoplasmic lipid
droplets in matrix and surface coat appearance, has been observed.
The surface coat of these triacylglycerol containing structures,
termed micro lipid droplets (μLD), was similar to that of cytoplasmic
lipid droplets in enzyme and polypeptide composition. Morphological
evidence suggested that these small structures may originate from
rough endoplasmic reticulum (RER) and fuse with cytoplasmic lipid
droplets. Immunochemical studies showed homology of certain proteins
among the rough endoplasmic reticulum, micro lipid droplets and
cytoplasmic lipid droplets, which supported the possibility of an endoplasmic reticulum origin of these droplets. The rate of
incorporation of [1-¹⁴C]-palmitate and [1,2,3-³H]-glycerol into
lipid of RER, μLD, CLD and MIG fractions suggested a possible
translocation pathway of triacylglycerols from the rough endoplasmic
reticulum to cytoplasmic lipid droplets. The micro lipid droplets
seem to provide triacylglycerols to support growth of cytoplasmic
lipid droplets. In addition, morphological evidence suggested that
these micro lipid droplets can be secreted directly in a manner
similar to cytoplasmic lipid droplets, providing for the small lipid
globules in milk. Little is known concerning the biochemical processes
of milk lipid secretion but it is thought that butyrophilin, a
glycoprotein found in milk lipid globule membrane, may play a role.
After treatment of mammary epithelial cells with tunicamycin,
butyrophilin content of this membrane is reduced. Thus a method for
the study of the physiological role of this glycoprotein is proposed.Master of Science
5
Bandegi, Sanaz. "INTERACTION OF FLUORESCENT LIPID DYES WITH LIPID VESICLES AND SUPPORTED LIPID BILAYERS AND THEIR APPLICATIONS." Diss., Temple University Libraries, 2019. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/584744.
Full textAbstract:
ChemistryPh.D.
Lipophilic dye probes are widely used for labelling of cells, organelles, liposomes, viruses and lipoproteins. The lipophilic dye diffuses in the membrane and stains the cell and cells even tolerate the lipophilic dye in high concentration. The fluorescence of styryl dyes increases after insertion into the hydrophobic environment of the lipid membrane compared their fluorescence in the aqueous phase solution. The alkyl chains of the fluorescent styryl dye probe insert into membranes and are used to understand their biophysical properties and their behavior in lipid bilayers. The mechanism of incorporation of the dyes into cell membranes, or vesicle model systems, is not resolved. In this study we used a modified dialkylaminostyryl fluorescent lipid, 4-(4-(dihexadecylamino)styryl)-N-methylpyridinium iodide (DiA), replacing the I- counterion with the Cl- anion to make DiA-Cl increase hydration of the polar head and to enable self-assembling in water and formation of vesicles. Vesicles composed of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine)/DiA, DPPC (1,2-dipalmitoyl-sn-glycero-3- phosphatidylcholine) /DiA, DSPC (1,2-distearoyl-sn-glycero-3- phosphatidylcholine) /DiA, DMPE (1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine)/DiA, DPPE (1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine)/DiA and DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine)/DiA have been prepared in mole ratios between 100/0 to 0/100, in order to investigate the effects of chain length and headgroup type on chain packing and phase separation in these mixed amphiphilic systems, using nanocalorimetry, dynamic light scattering and fluorescence data, as well as confocal laser scanning microscopy (CLSM) and cryo-transmission electron microscopy (Cryo-TEM). In addition, we report the self-assembly of DiA-Cl, to form H-aggregates of lipid bilayers in aqueous solution, beyond a critical vesicle concentration. Lipid bilayers can be fused onto silica nanoparticles (NPs) to form supported lipid bilayer (SLB)-NPs. (SLB)-NPs have a varous interdisciplinary applications from medicine to environmental fields and agriculture sciences. Here, the lipids on the nanoparticles were used for two applications. One was to adsorb polycyclic aromatic hydrocarbons (PAHs) from the environment and the other was as vehicles for foliar delivery of nutrients to plants. Silica SLB nanoparticles can increase the solubility of Benzo[a]Pyrene (BaP) in order to extract the BaP from soil for in situ biodegradation. Initial studies were begun on the effect of foliar application of silica SLBs nanoparticles on plants. The SLBs to be used were prepared using both 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and DiA, in order to determine whether the lipid increased the entry of the silica into the plant leaves and whether the lipids also entered.
Temple University--Theses
6
Oldham, Alexis Jean. "Modulation of lipid domain formation in mixed model systems by proteins and peptides." View electronic thesis, 2008. http://dl.uncw.edu/etd/2008-1/r1/oldhama/alexisoldham.pdf.
Full text
7
Temprano, López Ana. "The lipin protein family in human adipocytes: lipid metabolism and obesity." Doctoral thesis, Universitat Rovira i Virgili, 2016. http://hdl.handle.net/10803/398025.
Full textAbstract:
Les lipins són una família conservada evolutivament de fosfatases de fosfatidat (PAP1) dependents de Mg2+, que generen diacilglicerol per a la síntesi de fosfolípids i triacilglicerol. En mamífers, la família consta de lipina-1, lipina-2 i lipina-3. Mentre en ratolins la mutació del gen Lpin1 causa lipodistròfia, les mutacions deletèries en el gen LPIN1 en humans no afecten la distribució del greix. No obstant, persones amb diabetis tipus 2 mostren nivells reduïts de l'expressió de LPIN1 i de l'activitat PAP1. Aquesta tesi estudia el paper de les lipins en el teixit adipós humà, la adipogènesi i la lipòlisi. Descobrim que la expressió de gens i proteïnes lipin és alterada en el teixit adipós de les persones amb diabetis tipus 2. Silenciant cada membre de la família lipin en la línia cel•lular humana de preadipòcits del síndrome Simpson-Golabi-Behmel (SGBS), mostrem que mentre que els tres membres tenen un paper en el primers estadis de l’adipogènesi, els preadipòcits silenciats de lipin es diferencien i acumulen lípids neutres, la qual cosa condueix a la hipòtesi de l'existència de vies alternatives per a la síntesi de triacilglicerol en adipòcits humans quan es reprimeix l'expressió de les lipin. Les lipin participen també en el reciclatge d'àcids grassos alliberats mitjançant la via lipolítica. Després de la inducció de la lipòlisi, les lipines són defosforilades i es desplacen a la membrana del reticle endoplasmàtic, on exerceixen la seva funció enzimàtica. Aquesta activació és induïda pels àcids grassos alliberats i s'inverteix amb la presència d’albúmina o triacsin C. La inducció d’adipòcits silenciats de cada lipina demostra el seu paper en el metabolisme dels lípids neutres. En resum, les lipin semblen no tenir un paper imprescindible en la adipogènesi humana però sí poden comprometre el reciclatge d'àcids grassos, important per a la homeòstasis lipídica.Las lipinas son una familia de fosfatasas de fosfatidato (PAP1) dependientes de Mg2+ evolutivamente conservadas, que generan diacilglicerol para la síntesis de fosfolípidos y triacilglicerol. En mamíferos, la familia consiste en lipina-1, lipina-2, y lipina-3. Mientras en ratones la mutación del gen Lpin1 causa lipodistrofia, las mutaciones deletéreas en el gen LPIN1 en humanos no afectan a la distribución de grasa. Sin embargo, los individuos con diabetes tipo 2 manifiestan niveles reducidos de expresión de LPIN1 y de actividad PAP1. En esta tesis doctoral se estudia la función de las lipinas en el tejido adiposo humano, la adipogénesis y la lipólisis. Descubrimos que la expresión génica y proteica de las lipinas está alterada en el tejido adiposo de individuos con diabetes tipo 2. La depleción de cada miembro de las lipinas en la línea celular humana de preadipocitos del síndrome Simpson–Golabi–Behmel (SGBS), mostró que, a pesar de que los tres miembros tienen un papel en la adipogénesis temprana, los adipocitos deplecionados de lipinas se diferencian y acumulan lípidos neutros, llevándonos a la hipótesis de la existencia de vías alternativas para la síntesis de triacilglicerol en adipocitos humanos cuando la expresión de las lipinas es reprimida. Las lipinas también intervienen en el reciclaje de los ácidos grasos liberados por la vía lipolítica. Tras la inducción de la lipólisis, las lipinas son defosforiladas y se desplazan a la membrana del retículo endoplásmico, donde ejercen su función. Esta activación es inducida por los ácidos grasos liberados, y revertida con albúmina o triacsin C. La depleción de cada lipina en adipocitos SGBS y posterior inducción de la lipólisis, demuestra su papel en el metabolismo de lípidos neutros. En resumen, las lipinas parecen no tener un papel indispensable en la adipogénesis humana pero sí comprometer el reciclaje de ácidos grasos, importante para la homeostasis lipídica.
Lipins are evolutionarily conserved Mg2+-dependent phosphatidate phosphatases (PAP1) that generate diacylglycerol for phospholipid and triacylglycerol synthesis. In mammals the Lipin family consists of lipin-1, lipin-2 and lipin-3. Whereas mutations in the Lpin1 gene cause lipodystrophy in mouse models, LPIN1 deleterious mutations in humans do not affect fat distribution. However, reduced LPIN1 expression and PAP1 activity have been described in participants with type 2 diabetes. In this doctoral thesis we investigate the roles of all lipin family members in human adipose tissue, adipogenesis and lipolysis. We found that adipose tissue gene and protein expression of the lipin family is altered in type 2 diabetes. Depletion of every lipin family member in a human Simpson–Golabi–Behmel syndrome (SGBS) pre-adipocyte cell line showed that even though all members alter early stages of adipogenesis, lipin-silenced cells differentiate and accumulate neutral lipids, pointing to the hypothesis of alternative pathways for triacylglycerol synthesis under repression of lipin expression. Lipins also have a role in the recycling of the fatty acids released by the lipolytic pathway. They become dephosphorylated upon lipolytic induction, and translocate to their active site, the endoplasmic reticulum membrane. This activation is induced by fatty acids and reversed with albumin or triacsin C. Depletion of every lipin member and subsequently stimulation of lipolysis in SGBS adipocytes revealed a role for lipins in neutral lipid metabolism. Overall, our data support that lipins may not have an indispensable role in adipogenesis, but their depletion compromise fatty acid recycling and lipid homeostasis.
8
Carr, Neil Owen. "Lipid binding and lipid-protein interaction in wheat flower dough." Thesis, University of Reading, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293285.
Full textAbstract:
A study of lipid CClIplexirq in wheat floor ck:ujl has been made in an att:en¢ to explain the decrease in lipid extractability occurrin;J on dough developnent. '!be involvement of dough protein in this process has been assessa:i am new concepts have been evaluatai in the light of the known functionality of lipids in breadInakinI. PUblished W'Ork has irx:ticata:l that low IIDlecular \¥eight gluten proteins (ligolins) have a highly specific function in bin:ti.rg lipid. USl.rxJ similar fractionation methods to the plblished \¥Ork, it was possible to confirm this protein-lipid associaticn, although detergent cx:mtamination was d:JseIved followin;J the experimental procedure. It was sham that protein-lipid associaticn developed only in the preserx=e of detergent, whien led to a questionin;J of the pI'O{X)SeCi lipid bi.n::tin;J role of these low mlecular \¥eight proteins. It was also shown that the use of certain organic solvents can be unsatisfactory in the stlrly of protein-lipid interaction in dough. Fractionation by dilute acid provided evi~ that the 'baJnj' lipids of gluten were primarily in high mlecular \¥eight form, represented at least in part by a lip:JSaDal dispersion, whien were reasoned to be eri:e:tied within the gluten J'le'bvork in a oon-specific way. It was corcl.uled that interaction bet\¥een protein am such interactive lipid rmses ccW.d be responsible for the biniin:J of lipid durin;J dough develq:ment. Further sttnies are reported ~ the infll.lelDa of short:eni.n:J fat on lipid biniin;J. While there was sane in:lication that hard fat functionality was linked to an ability to maintain a critical pool of 'free' polar lipid, further work is required to investigate this early tentative CXl'd.usion. 'lhese stmies have been di srussed against a background of published WOrk, which has led to speculations al the nature and signifi~ of lipid b~ in the breadInakinI process. -
9
Reeder, Brandon Jon. "Reactions of lipid and lipid hydroperoxides with myoglobin and lipoxygenase." Thesis, University of Essex, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265191.
Full text
10
PERISSINOTTO, FABIO. "Lipid raft formation and lipid-protein interactions in model membranes." Doctoral thesis, Università degli Studi di Trieste, 2018. http://hdl.handle.net/11368/2919798.
Full textAbstract:
The biological membranes of eukaryotic organisms contain functional, highly dynamic nano-domains called "lipid rafts" (LRs) which are enriched in cholesterol, sphingolipids and GPI-anchor proteins. They are involved in several biological processes which implicate or are mediated by the plasma membrane. Moreover, LRs seem to have a critical role in the onset of some neurodegenerative diseases such as the Alzheimer’s disease (AD), Parkinson’s disease (PD) and Prion protein disorders. In the last two decades, the complexity of studying such domains in living cells has caused a growing interest in the use and design of artificial membrane models, which mimic the structure and composition of biological membranes. In this context, I promoted the formation and investigated the properties of lipid raft domains in artificial lipid bilayers by exploiting Atomic Force Microscopy (AFM). I compared two different fabrication methods for the production of artificial lipid bilayers, the drop-casting and the direct vesicle fusion techniques. I started from one-component lipid membranes and I progressively moved towards more complex models, as binary and ternary lipid compositions, in order to study the main LRs features in relation to specific biological phenomena, such as protein-lipid interactions involved in particular pathological diseases. The direct vesicle fusion method appeared to be the most suitable approach in term of reproducibility, stability and control of lipid composition. I took advantage from this method for carrying out a morphological characterization of raft-like model membranes composed by phosphocoline (DOPC), sphingomyelin (SM) and cholesterol focusing in particular on lipid phase behavior. Membranes exhibited the coexistence of two lipid phases, the fluid phase made by DOPC, and the solid-ordered phase made by SM and cholesterol, the latter resembling raft-like domains.
With selected 3-component lipid systems, I then investigated the distribution of GM1 ganglioside, a LR marker, into my system, demonstrating its preferential localization in the nano-domains and highlighting the feasibility and versatility of model membrane technology. For the first time, I studied the binding of synthetic full-length Prion protein (PrPc), carrying a C-terminal membrane anchor (MA), to LRs domains. The conversion of PrPc into the scrapie isoform PrPsc, which displays high propensity to aggregate leading to cytotoxicity, has been reported to take place into LRs and to be influenced by lipid-anchors. I demonstrated with this study the propensity of this protein to specifically target LR domains of my artificial systems, observing an aggregation process occurring even at low protein concentrations. A comparative analysis with PrPc lacking of MA is however required to assess the role of lipid-anchor into the protein distribution and aggregation.
Finally, in the last part of my research I focused on the study of the role of iron ions in the interaction between alpha synuclein (αS) and lipid membranes. αS is the central protein of PD and the presence of amyloid αS fibrils is the main pathological hallmark of the disease. By AFM in combination with attenuated total reflectance infrared (ATR-IR) spectroscopy, I compared the structural behavior of the wild-type (wt) and a mutant form of αS (A53T) in presence of Fe2+ ions and the effect of the iron ions on the interaction with my artificial membrane, and specifically with LRs.
11
Danial, John Shokri Hanna. "Imaging lipid phase separation on droplet interface bilayers." Thesis, University of Oxford, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711943.
Full text
12
Blakeston, Anita Catherine. "Biomimetic lipid bilayers." Thesis, University of Leeds, 2015. http://etheses.whiterose.ac.uk/11531/.
Full textAbstract:
The aims of the collaboration project, of which this project plays a key part, are to establish a new field of “low-dimensional chemistry” in order to synthesize manipulate and characterise the components of the photosynthetic system of Rhodobacter Sphaeroides. At a fundamental level, the physical processes involved in membrane biochemistry are to be investigated. Specifically, the environment in which the light harvesting components are found, their structure and function, including proton gradient formation, diffusion mechanisms, electron transport and the molecular association between them were to be studied. “The ultimate goal of the collaboration project was the reconstruction, on a chip in a synthetic low-dimensional system, of the complete photosynthetic pathway of the bacterium Rhodobacter Sphaeroides.” The creation of a homogeneous, fluid, polymer supported lipid bilayer to contain and maintain the integrity of these proteins, whilst under investigation, was a key part of the project. To create this successful system many polymer brush supports were examined, which were anionic, cationic and zwitterionic polyelectrolytes. Some were pH responsive and some were fully charged and did not change with pH. The properties of a range of lipid vesicles were studied using DLS, so that the zeta potential of the liposomes could be measured and then tuned specifically to be attracted to the oppositely charged polymer brush surfaces. It was found that at very low charge (a zwitterionic lipid vesicle or surface) no vesicles were attracted. At very high charge (a highly cationic or anionic polymer or lipid vesicle) vesicles were attracted to the surface, but remained intact and did not fuse to form a bilayer. These highly charged combinations of surfaces and vesicles created an intriguing “de-quenching halo” effect, which is worthy of further investigation. At a specific point of low to mid-charge interaction a fluid bilayer was formed on a brush which had a surface of low charge and was interacting with a charged vesicle. The successful polymer brush support was created using a short novel amino acid polycysteine methacrylate brush, which is pH responsive and can be micro-patterned. The vesicles used were composed of 25 mol % DOTAP, a cationic lipid, in combination with a zwitterionic POPC lipid. The diffusion coefficient of the bilayer deposited on the brush was measured using FRAP and found to match the rates measured for lipid bilayers on glass, which is considered to be the “standard” for comparison. The mobile fractions also compared very well to this standard. AFM scans showed a homogeneous surface and break-through force measurement confirmed a bilayer of 5 nm in thickness, as expected for a single bilayer. Attempts were subsequently made to incorporate proteins into this system by a number of methods, including creating proteoliposomes containing light harvesting components from the Rhodobacter Sphaeroides. The most promising of these was the development of a “one-step detergent depletion method” for creating a solubilised bilayer, adding protein and rinsing away the detergent in a single experiment. The characterisation of the system by TIRF, dark field and AFM microscopy was indicating success and paves the way for future work. In testing the polymer brushes as candidates for supporting a lipid bilayer, one with the potential to be used to create compartments in a corral for segregating the individual protein components of a light harvesting bacterium was also confirmed. This protein and lipid resistant Poly(2-(methacryloyloxy)ethyl phosphorylcholine), will facilitate the study of their function, by micro-patterning. In conjunction with the PCysMA this system has the potential be used to create corrals between these compartments which allow the free movement of ions between the proteins. The long term goal is to generate energy following light absorption by the proteins. The project is truly multidisciplinary and has presented the opportunity for collaboration between researchers in the disciplines of physics, chemistry and biology. The work presented here combines knowledge of membrane biophysics with polymer chemistry, and protein biochemistry.
13
Zhang, Tejia. "Discovery of bioactive lipids and lipid pathways in cell death and disease." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11483.
Full textAbstract:
Apoptosis is an intricately regulated cellular process required for the health and homeostasis of living systems. The mitochondrial apoptotic pathway depends on the BCL-2 family of pro- and anti-apoptotic members whose interactions regulate cell fate. BAX and BAK are key pro-apoptotic proteins required for mitochondrial permeabilization during apoptosis. While the mitochondrial death program relies heavily on its protein components, evidences support equally crucial roles for lipids and lipid metabolism in promoting or hindering apoptosis at the mitochondria. To gain insight into the interplay between lipids and BCL-2 proteins we used a liquid chromatography (LC)-mass spectrometry (MS)-based comparative lipidomics approach to uncover lipid changes in the absence of BAX and/or BAK. Our analysis revealed novel functions for BAX and BAK in inflammation and ceramide metabolism. A targeted LC-MS workflow was also developed for characterization of a novel lipid class involved in type 2 diabetes. Targeted LC-MS revealed altered oxysterol metabolism following perturbation of the Sonic hedgehog pathway. Taken together, our findings demonstrate interesting connections among lipids, cell death and disease.Chemistry and Chemical Biology
14
Subramaniam, Varuni. "Preparation and Characterization of Novel Lipid and Proteolipid Membranes from Polymerizable Lipids." Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/194889.
Full textAbstract:
The work described here has focused on two types of supramolecular assemblies, supported lipid bilayers (SLBs) and giant vesicles (GVs) from polymerizable lipids. SLBs are explored extensively as structural models in biophysical studies of cell membranes and biosensor coatings. With regard to implementation as biocompatible scaffoldings for receptor-based molecular devices, fluid SLBs lack chemical, thermal and mechanical stability as lipids are self-organized by weak, noncovalent forces. One possible solution is to use synthetic lipid monomers that can be polymerized to form robust bilayers. A key question is how polymerization affects transmembrane protein structure and activity. Specifically it is unclear if lipid cross-linking can be achieved without adversely affecting the activity of incorporated proteins. In this work the effect of lipid polymerization on transmembrane protein activity was studied with rhodopsin. The protein was reconstituted into SLBs composed of polymerizable lipids, bis-SorbPC, bis-SorbPC:mono-SorbPC, bis-DenPC and bis-SorbPC:mono-SorbPE. Rhodopsin photoactivity was monitored using plasmon waveguide spectroscopy. The results show that reconstitution of rhodopsin into SLBs composed of phosphatidylcholine with the polymerizable moiety in the acyl chain terminus, followed by photoinduced cross-linking of the lipids, does not significantly perturb protein function. A possible explanation is that a bilayer with relatively low Xn retains sufficient elasticity to accommodate the membrane deformation that accompanies the conformational change associated with rhodopsin photoactivation when polymerized in the acyl chain terminus. GVs have diameters ranging from several to few hundred micrometers and thus can be observed by optical microscopic methods. This allows manipulation of individual vesicles and observation of their transformations in real time. GVs have attracted attention as microcontainers for enzymes and drugs, and as biosensors. With the aim of increasing stability for these types of applications, GVs were prepared from synthetic dienoyl lipids that can be polymerized to form robust vesicles. The stability of these vesicles after polymerization was investigated by surfactant treatment, drying and rehydration, and temperature variations. The structure of poly(GVs) was largely retained under these conditions which destroy unpolymerized vesicles. Permeability studies on poly(GVs) suggests that they could be potentially used in a variety of technological applications, including sensors, macromolecular carriers, and microreactors.
15
McClinchie, Elizabeth A. "Homologs of Mammalian Lysosomal Lipase in Arabidopsis and Their Roles in Lipid Droplet Dynamics." Thesis, University of North Texas, 2017. https://digital.library.unt.edu/ark:/67531/metadc1062826/.
Full textAbstract:
Lipid droplets (LDs) are organelles with many functions in cells and numerous protein interactors facilitate their biogenesis, maintenance, and turnover. The mammalian lipase responsible for LD turnover during lipophagy, LipA, has two candidate homologs in Arabidopsis: MPL1 and LIP1. One or both of these plant homologs may function in a similar manner to mammalian LipA, providing an LD breakdown pathway. To test this hypothesis, wild type (WT) Arabidopsis plants, MPL1 over-expressing (OE) mutants, and T-DNA insertion mutants of MPL1 (mpl1) and LIP1 (lip1) were examined for LD phenotypes in normal conditions and in environments where LD numbers are known to fluctuate. Plants to be imaged by confocal microscopy were exposed to heat stress and wounding to increase LD accumulation, senescence was induced in leaves to deplete lipids, and LDs were imaged throughout the day/night period to observe their diurnal regulation. The mutation of both MPL1 and LIP1 lead to an increase in LDs within the leaf mesophyll cells, although the spatial distribution of the LDs differed between the two mutants. mpl1 mutants had disrupted diurnal regulation of their LDs, but lip1 mutants did not. Alternately, lip1 mutants retained LDs during dark-induced senescence, and mpl1 mutants did not. Together these results suggest that MPL1 and LIP1 are likely both important for LD dynamics; however they appear have roles in different aspects of LD accumulation and turnover.
16
Garton, Natalie Jane. "Investigation of mycobacterial lipid domains by use of fluorescent lipid probes." Thesis, University of Newcastle Upon Tyne, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244396.
Full text
17
Saeed, Suhur. "Lipid oxidation mechanisms and lipid-protein interactions in frozen mackerel (Scomber scombrus)." Thesis, University of Surrey, 1998. http://epubs.surrey.ac.uk/843251/.
Full textAbstract:
Atlantic mackerel (Scomber scombrus) is a pelagic fish widely distributed along the Northern coast of Great Britain. The lipid content of mackerel was found to be about 13% of the total body weight and 50% of total fatty acids were eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (fatty acids which are reported to reduce the concentration of plasma triglycerides, LDL (low density lipoproteins) and cholesterol in humans and animals). The proximate analysis also showed that mackerel is a good source of protein (20% w/w). The poly unsaturated fatty acids (PUFA) are prone to oxidation during frozen storage leading to rancidity and protein damage. Thus the objective of this project was to prolong the shelf-life of mackerel by controlling and understanding lipid oxidation mechanisms. HPLC, GCMS and 13C NMR spectroscopy were used for the first time to monitor the production of hydroperoxides and their secondary products in fish matched pairs of mackerel fillets were stored at either -20°C or -30°C. In addition fillets were also stored with or without different antioxidants at -20°C. The development of lipid oxidation products were recorded for up to 24 months. The oxidation products identified were mixtures of alcohol derivatives of hydroperoxides, namely: 13-hydroxy-9-trans, 11-cis-octadecadienoic, 13-hydroxy-9-trans, 11-trans-octadecadienoic, 9-hydroxy-10-cis, 12-transoctadecadienoic and 9-hydroxy-10-trans, 12-transoctadecadienoic acids. The amount of hydroxides produced were higher in fillets stored at -20°C compared with fillets stored at -30°C. Similarly, the hydroperoxides produced were considerably higher in samples stored without antioxidant than in fillets stored with vitamin E. In this study the transfer of radicals from lipid oxidation to proteins and subsequent formation of protein-cross-links has been reported for the first time. The interaction between lipids and proteins were examined by both ESR and fluoroscence spectroscopy. A central esr free radical (g )signal was observed in both simple systems (methyl linoleate and pure amino acids) and complex systems (fish lipid and pure proteins (lysozyme, ovalbumin) or fish protein (myosin)). The esr signal reached a maximum within a week and then started to decline and with a concomitant increase in a pinkish yellow chromogen. This chromogen which was soluble in organic solvent and fluoresced at an excitation wavelength 360 nm and emission wavelength 420 nm and indicated the formation of protein cross-links. Synthetic (BHT, BHA) and natural (vitamins E, C) antioxidants were capable of preventing both the radical transfer and protein cross-linking. In this study lipoxygenase was isolated from mackerel flesh and its involvement in lipid oxidation mechanism was established. The molecular weight of partially purified lipoxygenase was 119,000 Daltons. This enzyme was capable of oxidising arachidonic acid to 12-hydroeicosatetraenoic acid (12-HETE), which was identified by HPLC. This 12-HETE was absent in pure arachidonic acid and in samples to which boiled enzyme was added. Conventional inhibitors, synthetic and natural antioxidants also inhibited the formation of 12-HETE, indicating the importance of lipoxygenase in fish lipid oxidation. During frozen storage, protein solubility decreased and the texture deteriorated in Atlantic mackerel stored for 3, 6, 12 and 24 months at -20°C and -30°C. There was an increase in peroxide value and TBARS; decrease in myosin ATPase activity a decrease in myofibrillar protein solubility in high salt concentration as well as formation of high molecular weight aggregates which showed low thermal stability and high G' and G" modulus values. There were significant differences (P < 0.01) between samples stored at -20°C and -30°C, with greater deterioration evident in samples stored at -20°C. Similarly, there were significant differences (P < 0.01) between samples stored with and without antioxidants; the samples stored without antioxidants deteriorated faster than samples stored with antioxidants. This suggests the involvement of lipid oxidation products in protein deterioration during frozen storage.
18
Bonzom, Pascale Marie Andree. "High resolution NMR applied to lipid analysis and lipid based drug design." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300537.
Full text
19
Ntola, Chifundo Nyasha Michelle. "Solid lipid matrices for delivery of laundry actives and lipid membrane transport." Thesis, Durham University, 2017. http://etheses.dur.ac.uk/12027/.
Full textAbstract:
The work presented in this thesis reports the preparation and characterisation of novel solid lipid microparticle (SLM) and solid lipid nanoparticle (SLN) systems for applications in delivery of laundry actives and transport of electroactive substances into lipid membranes. The SLM and SLN systems studied are: silicone-loaded SLM, dye-loaded SLM, dual-active SLM (both silicone and dye) and ferrocene-loaded SLN (Fc-SLN). Silicones are used as fabric softeners in laundry applications and dyes are used to enhance the hue of fabrics. The incorporation of two actives into one, dual-active SLM, is a concept that could enable compact formulation and optimized formulation manufacture. The ferrocene-loaded SLN system represent the group of electroactive nanoparticles that could potentially find applications in biosensors, targeted delivery and other biomedical applications. The SLM and SLN systems were prepared using lauric acid as the lipid matrix. Silicone-loaded SLM systems were prepared using solvent-assisted methods with either ethanol or n-hexane as the solvent. They were stabilized with a combination of a primary alcohol ethoxylate (C14-15) (neodol 45-7) and polysorbate 80 (tween 80) as surfactant/co-surfactant). The silicones used were: polydimethylsiloxane (PDMS)(10,000 cST and 100,000 cSt), terminal amino-functionalised silicone (TAS) and a tertiary amino-functionalised silicone (PK10). The dye-loaded SLM systems, incorporating Coomassie Brilliant Blue R (CBB or BB) and ethyl violet (EV, Basic Violet 4) as hueing dyes were prepared using the double emulsion method, also descriptively known as the water-in-oil-in-water (w/o/w) emulsion method. The inner emulsion, w/o was stabilized using a low HLB surfactant, Brij 80 and the outer emulsion o/w was stabilized using a high HLB surfactant, tween 80. For the dual-active SLM system, PK10 silicone was added to the lipid phase before emulsification. The Fc-SLN system was prepared using the solvent emulsification/evaporation method. The surfactants used were poloxamer 188 and tween 80. The lipid membrane systems used were: solid-supported self-assembled monolayer (SAM) and tethered bilayer lipid membrane. The SAM was prepared by chemisorption of a thiolipid, 1,2-dipalmitoyl-sn-glycero-phosphothioethanol (DPPTE) onto a gold surface. Self-assembled monolayers were used as a lower leaflet or tether for the BLM system; an upper leaflet of 1-palmitoyl-2-oloeyl-sn-glycero-3-phosphocholine (POPC) was added by vesicle fusion. The characterisation and penetration of Fc-SLN into lipid membranes was studied using electrochemical methods such as cyclic voltammetry (CV), differential pulse voltammetry (DPV), electrochemical impedance spectroscopy (EIS) and Resonance Enhanced Surface Impedance (RESI). The SLM and SLN systems where characterised using laser diffraction and dynamic light scattering (DLS) for particle size analysis, optical microscopy and electron microscopy for morphology and particle size, small angle X-Ray Scattering (SAXS) and differential scanning calorimetry (DSC) for crystallinity and structural arrangement and chemical analysis using FTIR, solid state NMR and TGA.
20
Nikolaus, Jörg. "Hemifusion and lateral lipid domain partition in lipid membranes of different complexity." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2011. http://dx.doi.org/10.18452/16437.
Full textAbstract:
Die Fusion von Membranen erfordert die Verschmelzung von zwei Phospholipiddoppel-schichten, wobei dies über dieselben Zwischenschritte abzulaufen scheint. Eine lokale Störung (‚Stalk’) stellt eine erste Verbindung der äußeren Membranhälften dar, die anschließend lateral expandiert und ein Hemifusionsdiaphragma (HD) bildet. Das Öffnen einer Fusionspore im HD führt zur vollständigen Fusion. Mittels konfokaler Mikroskopie wurde die Fusion von Giant unilamellar vesicles (GUVs) mit negativ geladenen Lipiden und transmembranen (TM) Peptiden in Anwesenheit von zweiwertigen Kationen beobachtet, wobei die Peptide bei der HD Entstehung völlig verdrängt wurden. Eine detaillierte Analyse zeigte, dass es sich bei diesem Mikrometer-großen Bereich um ein HD handelt, dessen Größe von der Lipidzusammensetzung und Peptidkonzentration in den GUVs abhängt. Laterale Lipiddomänen gelten als entscheidend für Signal- und Sortierungsprozesse in der Zelle. Liquid ordered (Lo) Domänen in Modellsystemen wie GUVs ähneln den mit Sphingo-lipiden und Cholesterol angereicherten biologischen Raft-Domänen, allerdings scheinen Membraneigenschaften wie die Lipidpackung sich von biologischen Membranen zu unterscheiden. In diesem Zusammenhang wird die Sortierung des TM-verankerten Hemag-glutinin (HA) des Influenzavirus und von lipidverankerten Ras-Proteinen in GUVs wie auch in abgelösten Plasmamembran-Ausstülpungen (GPMVs) untersucht. HA Protein und TM-Pepitde von HA wurden ausschließlich (GUVs) bzw. vorwiegend (GPMVs) in der liquid disordered (Ld) Domäne gefunden. K-Ras wurde inmitten der Ld detektiert, während N-Ras zur Lo/Ld Grenzlinie diffundierte. Diese Ergebnisse werden im Zusammenhang mit den Unterschieden der Lipidpackung innerhalb der verschiedenen membranverankerten Systeme diskutiert. Es ist wahrscheinlich, dass die Bildung, Größe und Stabilität sowie die physikalischen Eigenschaften der Lipiddomänen in biologischen Membranen stark von Protein-Lipid-Wechsel-wirkungen beeinflusst werden.Membrane fusion is ubiquitous in life and requires remodelling of two phospholipid bilayers. Fusion likely proceeds through similar sequential intermediates. A stalk between the contacting leaflets forms and radially expands into a hemifusion diaphragm (HD) wherein finally a fusion pore opens up. Direct experimental verification of this key structure is difficult due to its transient nature. Confocal microscopy was used to visualize the fusion of giant unilamellar vesicles (GUVs) comprising negatively charged phosphatidylserine and fluorescent transmembrane (TM) entities in the presence of divalent cations. A complete displacement of TM peptides preceded full fusion. This is consistent with HD formation. Detailed analysis provided proof that the micrometer sized structures are in fact HDs. HD size is dependent on lipid composition and peptide concentration. Lateral lipid domain formation is believed to be essential for sorting and signalling processes in the cell. Liquid ordered (Lo) domains in model systems like GUVs resemble biological rafts enriched in sphingolipids and cholesterol, but their physical properties seem distinct from biological membranes as judged by e.g. lipid order and packing. In this context the sorting of TM anchored influenza virus hemagglutinin (HA) and different lipid anchored Ras proteins is studied in GUVs and giant plasma membrane derived vesicles (GPMVs). Authentic HA or the TM domain peptides were sorted exclusively (GUVs) or predominantly (GPMVs) to the liquid disordered (Ld) domains. Whereas K-Ras was found in the bulk Ld domains, N-Ras diffuses to the Lo/Ld interface. These results are discussed with respect to differences in lipid packing in the different membrane systems and regarding the membrane anchors and their hydrophobic matching. The results suggest that the formation, size and stability as well as the physical properties of lipid domains in biological membranes are tightly regulated by protein-lipid interactions.
21
Kamo, Tomoari. "Lipid membrane structure modulated by nonlamellar-forming lipids and interaction with amphipathic peptide." 京都大学 (Kyoto University), 2007. http://hdl.handle.net/2433/137121.
Full text
22
Covey, Scott D. Trigatti Bernardo L. "Carrier mediated lipid transport /." *McMaster only, 2003.
Find full text
23
Henderson, Erron James. "Lipid peroxidation by myeloperoxidase." Thesis, University of Canterbury. Zoology, 1998. http://hdl.handle.net/10092/6850.
Full textAbstract:
The oxidative modification of low density lipoprotein (LDL) is a requirement for the development of atherosclerosis. Heinecke's group has shown immunologically that myeloperoxidase (MPO) is present in human atherosclerotic lesions, both extracellularly and intracellularly (Daugherty et al., 1994). The enzyme MPO has a potent oxidising potential and is responsible for a large number of the reactants produced during the immune response (Weiss, 1989). Therefore, the neutrophil enzyme MPO has recently been implicated in in vivo LDL oxidation.
A few studies exist which suggest that MPO is capable of peroxidising lipids and free fatty acids directly via its peroxidase cycle (Hazell et al., 1994; Stelmaszynska et al., 1992). However, these studies only contain a small reference to this activity. Thus, it is not yet conclusively established whether MPO alone is capable of initiating lipid peroxidation, the primary objective of this study.
The present study has demonstrated that myeloperoxidase and its model peroxidase, horseradish peroxidase, are capable of initiating lipid peroxidation of linoleic acid micelles. This raises the possibility that MPO has a physiological role in the oxidation of LDL and consequently atherosclerosis. It also has implications for other inflammatory diseases where it is a possibility that MPO induced lipid peroxidation may mediate tissue injury.
24
Blyth, Alison. "Lipid biomarkers in speleothems." Thesis, University of Newcastle Upon Tyne, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435638.
Full text
25
Daulton, Emma. "Biomimetic floating lipid membranes." Thesis, University of Bath, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.675722.
Full text
26
Sherratt, Anna Louise. "Lipid bodies in mycobacteria." Thesis, University of Leicester, 2008. http://hdl.handle.net/2381/30499.
Full textAbstract:
A survey of clinical samples revealed that LBs are a universal feature of tubercle bacilli in sputum. A number of conditions including hypoxia, Nitric Oxide (NO) exposure, pH, heat and cold shock were shown to promote LB formation in M. tuberculosis in vitro. The formation of LBs in NO exposed M. tuberculosis was shown to correlate with the level of antibiotic tolerance displayed by the population. Antibiotic tolerance was thought to be a result of transitory growth arrest; however attempts to assess the growth status of LB positive M. tuberculosis cells were unsuccessful. The morphology of LBs in mycobacteria varied according to the growth condition of the cell and may be due to a change in lipid composition. The mechanism by which LBs are formed in mycobacteria remains unknown; however, there was some evidence to suggest that it follows a scheme similar to that which has been previously demonstrated in Rhodococcus opacus. It was concluded that LB formation in mycobacteria may depend on a number of environmental factors, including conditions that promote growth arrest. The formation of LBs in M. tuberculosis may anticipate antibiotic tolerance. The presence of LBs in sputum tubercle bacilli may be used to assess treatment response in patients with tuberculosis; however, it remains to be shown that LB positive M. tuberculosis cells in vitro represent the physiological LB positive sputum bacilli.
27
Kilaru, Aruna. "Lipid Detection and Visualization." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/7731.
Full text
28
Martinez, Ortega Maria Eugenia. "Lipid metal organic networks." To access this resource online via ProQuest Dissertations and Theses @ UTEP, 2009. http://0-proquest.umi.com.lib.utep.edu/login?COPT=REJTPTU0YmImSU5UPTAmVkVSPTI=&clientId=2515.
Full text
29
Thorén, Klas. "Lipid-extracted bone grafts." Lund : Dept. of Orthopedics, University Hospital, Lund University, 1994. http://catalog.hathitrust.org/api/volumes/oclc/39676934.html.
Full text
30
Darroch, Peter Ian. "Lipid phosphate phosphatases : purification and investigation of their role in cellular lipid signalling." Thesis, University of Strathclyde, 2001. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=21171.
Full textAbstract:
Several isoforms of LPP have now been identified and cloned but remain to be purified. In the present study, a bacterial expression system was established and hexa- and deca-histidine epitope tagged-LPP1 and LPPla expressed in E. coli. In addition, a maltose binding protein (MBP) epitope tagged-LPP Ia was expressed in E. coli. Hexa- and deca-histidine LPP1 and LPPla, were partially purified using immobilised affinity chromatography. MBP-LPPla was expressed to higher levels than hexa- and deca-histidine LPP1 and LPPla in E. coli, most probably within insoluble inclusion bodies. In all cases, recovery of LPP activity was low. Membranes derived from HEK293 cells that stably over-express LPP I, LPP I a, LPP2 or LPP3 were used to demonstrate the differential hydrolysis of several molecular species of PA, LPA(18: 1), C8-CIP and SlP. Kinetic analysis using a multisubstrate assay system revealed that the LPP isoforms do not follow typical Michaelis-Menten kinetics towards most substrates under the assay conditions employed. The LPPs appear to show differential kinetics depending on the complement of substrates accessible to the enzymes. Stable over-expression of LPPI, LPPla, LPP2, but not LPP3, in HEK293 cells has previously been shown to attenuate the activation of ERK-1/2 by G-protein coupled receptors agonists such as SIP, LPA, PA and thrombin. The present study extended these observations by showing that basal growth rates were unaffected and that levels of mRNA transcript for the SIP, /EDGI receptor were reduced in the LPP stable cell lines but that this did not correlate with attenuation of the SIP-stimulated ERK-1/2 response. In addition, transient overexpression of LPPI, LPPIa and LPP2, but not LPP3 in HEK293 cells and GPASM cells also resulted in the attenuation of SIPinduced ERK-1/2 activation. Furthermore, transient transfection of a plasmid construct encoding the antisense sequence for LPP1 was also found to attenuate SIPinduced ERK-1/2 activation whereas the PMA-stimulated response was unaffected. Many questions remain to be fully answered in order to determine the physiological and pathophysiological. roles of the LPPs and the reason for the molecular diversity of the enzyme family.
31
Ding, Yuan [Verfasser]. "Lipid nanoparticles for topical delivery: solid lipid nanoparticles (SLN) & smartLipids / Yuan Ding." Berlin : Freie Universität Berlin, 2018. http://d-nb.info/1176632329/34.
Full text
32
Borthwick, Faye. "Studies on the role of 'start' lipid trafficking proteins in macrophage lipid homeostasis." Thesis, Glasgow Caledonian University, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.496152.
Full textAbstract:
Steroidogenic acute regulatory (StAR) related-lipid transfer (START) proteins (STARD1-STARD15) are suggested to play a role in cholesterol homeostasis and atherosclerosis, and are potential drug targets by virtue of their lipid binding domains. Members of the STARD1 subfamily (STARD1, STARD3) of lipid trafficking 'START' proteins can reduce macrophage lipid content and inflammatory status (STARD1; StAR), and traffic cholesterol from the endosomes (STARD3/MLN64) All of the 'START' family members were found to be expressed in human heart aorta, peripheral blood monocytes and human THP-1 monocytes, except testis-specific STARD6. Phorbol ester-Induced differentiation of THP-1 monocytes to macrophages (7 days) induced two-fold or greater Increases in gene expression of STARD4, STARDd, STARD9 and STARD14, whereas levels of STARD3 mRNA declined. Treatment with acetylated LDL increased gene expression of STARD4, STARD10, STARD12 more than two-fold, but levels of STARDl STARD2, STARD7, STARDd, STARD9 and STARD14 mRNA declined significantly.
33
Ng, Ai-Leng. "Comparisons of serum lipid levels and dietary lipid intakes of parents and children." Thesis, Virginia Tech, 1988. http://hdl.handle.net/10919/43259.
Full textAbstract:
Fifty-seven subjects from 14 families participated in a study designed to investigate similarities and differences between parents and children residing with them relative to their serum lipid levels and dietary lipid intakes. To participate, at least one of the parents needed to have a serum total cholesterol of at least 240 mg/dL.
Fasting blood samples obtained from the participants were analyzed for serum total cholesterol, HDL-C, LDL-C, and VLDL-C levels. Anthropometric measurements and blood pressure readings also were taken. Dietary records, questionnaires on lifestyle, health habits, health history, and nutrition knowledge were completed by the participants.
Correlation coefficients between serum total cholesterol and dietary cholesterol intakes of the fathers were 0.66 (p = 0.01) in all 14 families and 0.64 (p = 0.05) in the 11 families in which at least one parent had a family history of CHD. The values of the correlation coefficients of HDL-C and the intake of dietary cholesterol of the children for the 14 families and the 11 families were -0.36 (p = 0.07) and -0.55 (p = 0.01) respectively. A significant correlation was found between the dietary pattern of the parents and that of their children. The following correlation coefficients were found for the five families in which both parents had a fmaily history of CHD: 0.65 (p = 0.02) for total fat, 0.79 (p = 0.002) for saturated fat , and 0.59 (p = 0.04) for cholesterol.Master of Science
34
Addy, Victoria Louise. "The use of lipid hydrolases to target the lipid components of ovine skin." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711595.
Full text
35
Veatch, Sarah Louise. "Liquid immiscibility in model bilayer lipid membranes /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/9772.
Full text
36
Sturgeon, Raymond M. "Interplay between cations, anionic lipids, and lipid-protein interactions at the nicotinic acetylcholine receptor." Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28070.
Full textAbstract:
Mixtures of phosphatidylcholine (PC) and phosphatidic acid (PA) are particularly effective at stabilizing a functional nicotinic acetylcholine receptor (nAChR). To test whether the ability of PA to adopt both monoanionic and dianionic states plays a role in lipid-nAChR interactions, we monitored the ionization state of PA in nAChR-reconstituted membranes. In the presence of the nAChR, PA head groups in PC/PA 3:2 membranes are stabilized in the monoanionic state. Stabilization of monoanionic PA in nAChR-reconstituted membranes accounts for some of the observed increase in membrane gel-to-liquid crystal phase transition temperature (Tm) upon nAChR incorporation, possibly by nAChR-induced pH reduction at the membrane surface. Increasing concentrations of cations at the bilayer surface and diacylglycerol within the bilayer account for the remaining shift in membrane Tm observed upon nAChR incorporation. We conclude that the nAChR, which is a cation-selective ion channel, alters its environment through both cation concentration and enzymatic activity.
37
Prindiville, John S. "Circulating lipoproteins and tissue lipids: Effects of gemfibrozil on lipid metabolism in rainbow trout." Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28555.
Full textAbstract:
Lipids support crucial functions in teleost fish, including the production of energy; lipoproteins support the movement of lipids through the vascular system. The objective of this thesis was to determine if gemfibrozil (GEM), a mammalian PPARalpha agonist pharmaceutical, could alter the circulating lipoproteins and tissue lipid metabolism in the rainbow trout, Oncorhynchus mykiss.
Injections of GEM lowered the concentration of lipoproteins and changed their size distribution, lipid and fatty acid content. These changes were associated with an increased lipoprotein lipase transcript level but not activity. GEM increased liver size but did not affect its lipid content nor the activities or transcript levels of its PPARs and mitochondrial/peroxisomal enzymes.
This thesis provides evidence that the pharmacological effects of GEM are conserved across vertebrates. Furthermore, the decreased plasma lipids and altered lipoprotein composition demonstrated here may be relevant sublethal indicators of exposure to PPARalpha agonists present in the aquatic environment.
38
Herzog, Ronny. "Novel concepts for lipid identification from shotgun mass spectra using a customized query language." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-90497.
Full textAbstract:
Lipids are the main component of semipermeable cell membranes and linked to several important physiological processes. Shotgun lipidomics relies on the direct infusion of total lipid extracts from cells, tissues or organisms into the mass spectrometer and is a powerful tool to elucidate their molecular composition. Despite the technical advances in modern mass spectrometry the currently available software underperforms in several aspects of the lipidomics pipeline. This thesis addresses these issues by presenting a new concept for lipid identification using a customized query language for mass spectra in combination with efficient spectra alignment algorithms which are implemented in the open source kit “LipidXplorer”.
39
Mateos, Diaz Eduardo. "Etude par spectroscopie infrarouge (FTIR) des interactions de la lipase pancréatique apparentée de type 2 (PLRP2) avec les phospholipides et les sels biliaires." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4763.
Full textAbstract:
La lipase pancréatique apparentée de type 2 du cobaye (GPLRP2) hydrolyse une grande variété de substrats lipidiques. Elle montre cependant une sélectivité selon l’organisation supramoléculaire du substrat et la présence de surfactants comme les sels biliaires (NaTDC). Nous avons utilisé la spectroscopie infrarouge (FTIR) pour étudier les interactions entres les phospholipides (DPPC), les surfactants et la GPLRP2 dans des conditions expérimentales proches de celles du tractus digestif. Pour étudier l’étape d’adsorption indépendamment de l’hydrolyse, un variant inactif de GPLRP2 (S152G) a été produit. Diverses dispersions aqueuses de phospholipides ont été préparées : des vésicules multilamellaires (MLV), unilamellaires (LUV) et des micelles mixtes DPPC-surfactant. GPLRP2 hydrolyse le DPPC présent dans des micelles mixtes DPPC-NaTDC mais n’a aucune activité sur le DPPC en phase lamellaire ou présent dans des micelles DPPC-Triton X100. L’analyse par FTIR de l’interaction de GPLRP2 S152G avec le système DPPC-NaTDC montre des changements importants dans le désordre conformationnel et la mobilité des chaînes acyles, la déshydratation de l’interface, l’orientation des têtes polaires et leurs liaisons hydrogène. Aucun effet n’est observé avec les MLV, les LUV ou le système DPPC-Triton X100. Il y a ainsi une reconnaissance spécifique du DPPC dans les micelles mixtes avec les sels biliaires, en accord avec l’activité enzymatique de GPLRP2. Les changements du spectre IR pendant l’hydrolyse du DPPC par la GPLRP2 ont été suivis. Certaines caractéristiques attribuées à la formation de produits de lipolyse peuvent être utilisées pour une étude quantitative de la lipolyse par FTIRGuinea pig pancreatic lipase-related protein type 2 (GPLRP2) hydrolyzes a large set of lipid substrates, but displays however some selectivity depending on the supramolecular structure of substrate and the presence of surfactants like bile salts (NaTDC). We used Fourier transform infrared (FTIR) spectroscopy to study the interactions between phospholipids (DPPC), surfactants and GPLRP2 under conditions close to those of the GI tract. To study the adsorption step independently from hydrolysis, a GPLRP2 inactive variant (S152G) was produced. Various phospholipid dispersions were prepared: multilamellar (MLV) and large unilamellar vesicles (LUV) and mixed micelles with surfactants. GPLRP2 was found to hydrolyze DPPC present in mixed DPPC-NaTDC micelles but was inactive on DPPC vesicles and DPPC-Triton X100 micelles. FTIR analysis of GPLRP2 S152G interaction with the DPPC-NaTDC system showed a decrease in the conformational disorder and mobility of the acyl chains, a dehydratation of the interface, and changes in the orientation and H-bonding of DPPC polar head-groups. These effects were not observed with MLV, LUV and DPPC-Triton X100 micelles, thus indicating a specific recognition of DPPC in mixed phospholipid-bile salt micelles, in agreement with phospholipase activity measurements. Changes in the IR spectra during DPPC hydrolysis by GPLRP2 were monitored. Specific spectral features were associated to the production of lipolysis products and could be used for quantifying phospholipid lipolysis by FTIR
40
Petkevicius, Kasparas. "The role of macrophage intracellular lipid partitioning in glucose and lipid homeostasis during obesity." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/285429.
Full textAbstract:
Obesity-associated metabolic disorders are amongst the most prevalent causes of death worldwide. Understanding how obesity leads to the development of the Metabolic Syndrome (MetS) and cardiovascular disease (CVD) will enable the development of novel therapies that dissociate obesity from its cardiometabolic complications. Our laboratory views the functional capacity of white adipose tissue (WAT), the organ designed for safe lipid storage, as a key factor in the development of MetS and CVD. At a genetically-defined stage of the aberrant WAT expansion that occurs during obesity, adipocytes undergo a functional failure, resulting in an impaired control of serum free fatty acid (FFA) concentration. In such setting, FFAs and their metabolic derivatives accumulate in other organs, where they cause lipotoxicity, leading to the development of insulin resistance and CVD. We therefore aim to understand the pathophysiological mechanisms that induce adipocyte dysfunction. The past two decades of research have established the immune system as an important regulator of WAT function. The number of adipose tissue macrophages (ATMs), the most abundant immune cell type in WAT, increases during obesity, resulting in WAT inflammation. Multiple genetic and pharmacological intervention studies of murine models of obesity have assigned a causal link between ATM pro-inflammatory activation and WAT dysfunction. However, while the propagation of inflammation in ATMs during obesity has been extensively studied, factors triggering ATM inflammatory activation are less clear. Recently, our lab has observed lipid accumulation in the ATMs isolated from obese mice. Lipid-laden ATMs were pro-inflammatory, leading us to hypothesise that aberrant lipid build-up in macrophages triggers WAT inflammation during obesity. This thesis expands on the initial findings from our lab and describes two novel mechanisms that potentially contribute to lipid-induced inflammatory activation of ATMs. In chapter 3, the role of de novo phosphatidylcholine (PC) synthesis pathway during lipotoxicity in macrophages is addressed. The first part of the chapter demonstrates that lipotoxic environment increased de novo PC synthesis rate in bone marrow-derived macrophages (BMDMs) and ATMs, and that loss of rate-limiting enzyme in de novo PC synthesis pathway, CTP:phosphocholine cytidylyltransferase a (CCTa) diminished saturated FFA-induced inflammation in BMDMs. In the second part, I show that macrophage-specific CCTa deletion did not impact on the development of WAT inflammation or systemic insulin resistance, but had a minor benefitial effect on hepatic gene transcription during obesity. Chapter 4 develops on recent observations of interactions between sympathetic nerves and macrophages in WAT. In the first part of the chapter, I demonstrate that stimulating B2-adrenergic receptor (B2AR), the main receptor for sympathetic neurotransmitter norepinephrine in macrophages, enhanced intracellular triglyceride storage by up-regulating diacylglycerol O-acyltransferase 1 (Dgat1) gene expression in BMDMs. The second part of the chapter shows that macrophage-specific B2AR deletion did not modulate systemic glucose and lipid metabolism during obesity, but mice lacking B2ARs in macrophages demonstrated augmented hepatic glucose production on a chow diet. Furthermore, systemic B2AR blockade or macrophage-specific B2AR deletion in mice did not affect the thermogenic response to cold exposure. Chapter 5 includes the characterisation of B2AR stimulation-induced changes to the global cellular proteome of BMDMs, and a subsequent validation of the role of candidate transcription factors in regulating B2AR agonism-induced gene expression in BMDMs.
41
Cheong, Fei Ying. "Regulation of lipid signaling at the Golgi by the lipid phosphatases hSAC1 and OCRL1." [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:16-opus-71011.
Full text
42
Turenne, Eric D. "Lipid Mobilization In Exercising Salmonids." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37075.
Full textAbstract:
Animals rely on lipids as a major fuel for endurance exercise because they pack more joules per gram than any other fuel. However, in contrast to mammals, information on how the mobilization of lipids from endogenous stores is managed to meet the needs of energy metabolism in swimming fish is sparse. Information on in vivo rates of lipid mobilization in swimming fish has been limited to relatively low exercise intensities and has only been investigated in a single species. Therefore, the goal of my thesis was to address this paucity of information by quantifying lipolytic rate in rainbow trout during graded exercise and fatty acid mobilization in Atlantic salmon during prolonged endurance exercise.
In the first part of my work, I hypothesized that like mammals, rainbow trout stimulate lipolysis above resting levels to a peak with increasing work intensity, but subsequently lower its rate at high intensities when ATP production from carbohydrates becomes dominant. To test this hypothesis, I measured the rate of appearance of glycerol (Ra glycerol) in the blood (resulting from the breakdown of triacylglycerol (TAG)) of trout at rest (control) and during graded exercise from rest to Ucrit. Results showed that Ra glycerol in trout averaged 1.24 ± 0.10 µmol kg -1 min-1 and that this rate was unaffected by exercise of any intensity. These experiments revealed that rainbow trout do not modulate lipolysis during exercise. Furthermore, I calculated that baseline lipolytic rate was much higher in trout than in mammals and that this rate is in constant excess of the requirements of energy metabolism.
My second investigation focused on measuring fatty acid mobilization in Atlantic salmon. To date, the majority of studies on energy metabolism in salmonids have used rainbow trout as the ubiquitous model for salmonids. I postulated that domesticated rainbow trout may be far less impressive athletes than their wild anadromous form and other salmonids. In this regard, I proposed that studying energy metabolism in Atlantic salmon (even those from aquaculture) may help to deepen our understanding of the physiology of true long-distance migrant fish. To study the effects of prolonged endurance exercise on the mobilization of fatty acids from endogenous stores in these fish, I monitored the rate of appearance of fatty acids (Ra NEFA calculated from Ra Palmitate) in the blood during 72 hours of sustained swimming. I found that contrary to what has been previously described in rainbow trout, Ra Palmitate (and by proxy, Ra NEFA) is reduced by approximately 64% (from 0.75 ± 0.12 µmol kg-1min-1 to 0.27 ± 0.06 µmol kg-1min-1 and from 19.3 ± 7.8 µmol kg-1min-1 to 6.9 ± 2.0 µmol kg-1min-1 for Ra Palmitate and Ra NEFA, respectively) during prolonged endurance exercise in Atlantic salmon. However, like in trout, even this reduced rate of fatty acid mobilization exceeds the requirements of energy metabolism at rest and during swimming. While further experiments will be necessary, I speculated that this reduction in Ra NEFA may be caused by a partial inhibition of lipolysis to reduce the energetic cost of TAG:FA cycling and optimize fuel budgets during prolonged endurance exercise.
This thesis provides the first in vivo measurements of lipolysis during graded exercise in salmonids and the first in vivo measurements of fatty acid mobilization in Atlantic salmon. From the results mentioned above, I concluded that salmonids mobilize lipids in constant excess of the requirements for energy metabolism, possibly to allow for rapid reorganization of membrane phospholipids in response to changing environmental conditions. However, more anadromous and migratory phenotypes may rely on a tighter control of lipolysis to minimize the costs of substrate cycling and conserve energy on limited fuel stores.
43
Harczy, Martha. "Lipid mediators in lung anaphylaxis." Mémoire, Université de Sherbrooke, 1988. http://hdl.handle.net/11143/11716.
Full textAbstract:
Abstract: Arachidonic acid and PAF are released from the lungs during anaphyIaxis. The aim of this study is to describe the kinetics of the release of eicosanoids and to observe the effects of selected ihhibitors and a PAF antagonist on their release. Isolated lungs of previously sensitized animals were perfused via the pulmonary artery and challenged with ovalbumin. Prostaglandin E21 throraboxane B2, 6-keto prostaglandin F1? levels were determined in aliquots of effluents with radioimmunoassay and/or enzyme immunoassay techniques whereas leukotrienes B4 and D4 were measured by reverse-phase high performance liquid chromatography. In selected experiments 12-HHT and 12-keto HT were measured in the lung effluents. The peak release of eicosanoids from the lungs ensued approximately at 4-6 minutes after the initiation of anaphylactic shock. Perfusion of the lungs with aspirin, indomethacin decreased the formation of cyclooxygenase products and there was no significant change in the release of LTB4, LTD4. BW755C and ETYA at high concentrations reduced the release of all eicosanoids from the lungs as did high concentrations of FPL55712. An antagonist of PAF (BN52021) produced a dose dependent inhibition of prostaglandins, thromboxane and leukotrienes from the anaphylactic lungs. Perfusion of PAF in non-sensitized lungs produced a release of eicosanoids, however the magnitude of the release was negligible compared to that of the release in anaphylactic shock. A Vitamin E analog inhibited the release of LT-s while did not inhibit the release of PG-S and TxB2. These, results emphasize on the complex interactions regulating the synthesis of arachidonic acid metabolites and an indirect role of PAF has been suggested.||Résumé: L'acide arachidonique et le PAF sont libérés par le poumon durant le choc anaphylactique. Le but de la présente étude est d'analyser la cinétique de la libération d'eicosanoïdes, et d'observer les effets de plusieurs inhibiteurs et d'un antagonistes du PAF sur leur libération. Le poumon de cobaye sensibilisé a été perfusé via l'artère pulmonaire et stimulé avec l'ovalbumine. La prostaglandine E2, la thromboxane B2, la prostaglandine 6-ceto-F1? ont été déterminées dans les échantillons de l'effluent avec un essai radioimmunologique ou avec une technique d'essai immunologique enzymatique alors que les leucotriènes B4 et D4 ont été mesurées par chromatographie liquide à haute performance en phase inversée. Dans certaines expériences, le 12-HHT et le 12-ceto-HT ont été mesurés dans l'effluent pulmonaire. Le pic de libération des eicosanoïdes a été observé approximativement 4-6 minutes après le début du choc anaphylactique. La perfusion du poumon avec l'aspirine et l'indométacine a diminué la formation des produits de la cyclooxygénase et n'a pas modifié la libération de leucotriènes B4 et de leucotriènes D4. Le composé BW755C, le ETYA ainsi que le FPL55712 utilisés à fortes concentrations ont réduit la libération de tous les eicosanoïdes du poumon. L'antagoniste du PAF (BN52021) a produit une inhibition dose-dépendante de la libération de prostaglandines, de thromboxanes et de leucotriènes par le poumon anaphylactique. Lorsque les poumons de cobayes non-sensibilisés ont été traités avec des injections de PAF, nous avons noté la libération d'eicosanoïdes. Cependant, la libération d'eicosanoïdes stimulée avec ce médiateur lipidique était beaucoup moindre que celle observée au cours du choc anaphylactique. Un analogue de la vitamine E a inhibé la libération de leucotriènes alors qu'il n'a pas inhibé de libération de prostaglandines et de thromboxanes. Ces résultats mettent en évidence les interactions complexes qui interviennent au cours de la synthèse des métabolites de l'acide arachidonique et le rôle complexe du PAF dans les réactions d'hypersensibilité et inflammatoires.
44
Shilton, Catherine Margaret. "Corneal lipid deposition in anurans." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0020/NQ55639.pdf.
Full text
45
Hafez, Ismail Mahmoud. "Lipid polymorphism and intracellular delivery." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0021/NQ56555.pdf.
Full text
46
Raggers, René John. "Lipid translocation by multidrug transporters." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2001. http://dare.uva.nl/document/60218.
Full text
47
Derrien, Thomas. "Gold nanoparticle-lipid bilayer interactions." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86727.
Full textAbstract:
The interactions of ligand-capped gold nanoparticles with lipid bilayers are investigated. The properties determining the mechanism of nanoparticle interaction using synthetic membrane models are explored. First, a specific interaction, incorporation of nanoparticles into the bilayers, is examined using novel imaging and nanoparticle synthesis techniques. Mixed ligand capped gold nanoparticles are synthesized with assorted ligand arrangements in order to relate ligand composition and structure to interaction mechanism using a dye leakage assay. Finally, in vivo experiments are conducted using peptide labeled fluorescent gold nanoparticles in live HeLa cells. It was found that gold nanoparticles are capable of crossing lipid bilayers, implying energy-independent cellular uptake mechanisms may occur. It is concluded that the structure and composition of the protecting ligands are critical in determining the magnitude of bilayer disruption.L'interaction des nanoparticules d'or avec les bicouches lipidiques est présentée dans ce mémoire. Les facteurs influençant cette interaction ont été explorés en utilisant des bicouches lipidiques synthétiques. L'interaction due à l'incorporation des nanoparticules au sein des bicouches a été étudiée par des techniques d'imagerie. Un test de fuite de fluorophore a été employé afin de déterminer l'influence de la composition et de la structure des ligands protégeant les nanoparticules sur leur incorporation dans les bicouches de lipides. Pour cela, nous avons développer une synthèse de nanoparticules protégées par deux types de ligands. Des expériences in vivo ont été réalises avec des nanoparticules d'or fonctionnalisées avec des peptides ainsi que des fluorophores, mis en contact avec des cellules vivantes de type HeLa. Nous avons constaté que les nanoparticules d'or sont capables de franchir les bicouches lipidiques en utilisant des mécanismes indépendants d'énergie. Nous concluons que la structure et la composition des ligands protégeant les nanoparticules ont une grande influence sur la perturbation qu'elles induisent dans la structure des bicouches lipidiques.
48
Khatchadourian, Armen. "Lipid droplets under stressful conditions." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116901.
Full textAbstract:
Lipid droplets (LDs) are phylogenetically conserved and ubiquitous organelles with many cellular functions. In the last two decades, our understanding of LD biology and of their roles in physiological processes has increased dramatically. In addition, increasing evidence suggests that LDs are highly involved in inflammatory processes, and in metabolic disorders such as type 2 diabetes mellitus (T2DM). Despite such advancement, many aspects of LD biology and of their roles in health and disease remain unknown.The core of LDs is highly enriched with neutral lipids and these can be mobilized to provide metabolic energy. The phospholipid monolayer surrounding the LD core is associated with a wide variety of proteins, including structural and signaling proteins, as well as metabolic enzymes. While LDs may be induced by physiological stimuli such as dietary fatty acids, they can also be formed under stressful conditions, in the absence of such fatty acids. However, exactly how cellular stress leads to LD accumulation remains unclear. Our main objective is to understand the regulation of LD formation under stressful conditions, specifically oxidative stress, inflammation, and metabolic stress. We first investigated LDs in cells exposed to environmental stressors, namely cytotoxic metallic nanoparticles and reactive oxygen species. LD formation and expression of perilipin-2, a key structural LD protein, were highly increased in rodent cells exposed to these stress agents. Interestingly, supplementation with antioxidant N-acetyl cysteine or pharmacological inhibition of p38 mitogen activated protein kinase (MAPK) reduced stress-induced LD accumulation, suggesting that oxidative stress and p38 MAPK activation play a role in the induction of LD formation. Inflammatory leukocytes and macrophages contain a large number of LDs. While this phenomenon has been widely investigated in peripheral immune cells, its explanation remains elusive in immune cells of the central nervous system. We therefore investigated LD dynamics and regulation in microglia, the resident immune cells in the brain. We found that stimulation of microglia with toll-like receptor 4 (TLR4) agonist, lipopolysaccharides (LPS), increased LD formation and perilipin-2 expression in an Akt and p38 MAPK-dependent manner. Interestingly, LPS-induced LDs extensively colocalized with cytosolic phospholipase A2-α (cPLA2-α), a key enzyme involved in the synthesis of eicosanoids, which are inflammatory lipid mediators. Collectively, these findings imply that LD formation may contribute to increased eicosanoid synthesis in activated microglia and could be microglial biomarkers of inflammation in the central nervous system. To gain a better insight into the role of LDs in human pathology, we sought to examine alterations in LD metabolism in pancreatic tissue obtained from T2DM and obese individuals. Immunohistochemical studies revealed increased islet and extra-islet perilipin-2 expression in tissues from lean or obese T2DM donors, but not in non-T2DM obese donors, suggesting that the diabetic status, but not the obesity status, is a requirement for increasing perilipin-2 expression and LD formation. Gene expression analysis by RT-qPCR confirmed the increase in perilipin-2 expression and revealed significant alterations in several genes related to islet function, metabolism and antioxidant defense. These alterations seem to be consistently associated with obesity and T2DM and imply an adaptive and compensatory response to insulin resistance and metabolic stress. In summary, our studies show that LDs are an integral part of the adaptive cellular response to oxidative, inflammatory and metabolic stress. Perhaps, the most important challenge in LD research in the upcoming decade will be to determine how the subcellular lipid and protein composition of this organelle affects its function in different cells.Les gouttelettes lipidiques (GL) sont des organites phylogénétiquement conservées et impliquées dans plusieurs fonctions cellulaires. Durant les deux dernières décennies, notre compréhension des rôles biologiques et physiologiques des GL a augmenté de manière draconienne. Plusieurs observations suggèrent fortement que les GL jouent un rôle important dans l'inflammation, ainsi que dans les désordres métaboliques tels que le diabète de type 2 (DT2). Malgré cette avancée, plusieurs aspects de la biologie des GL et de leurs rôles dans des maladies demeurent méconnus.Le centre des GL est riche en lipides neutres qui peuvent se mobiliser et servir comme source d'énergie. La couche phospholipidique entourant le centre de la GL est associée à plusieurs protéines et enzymes métaboliques. Bien que les GL puissent être induites par des acides gras, elles peuvent aussi l'être dans des conditions de stress. Par contre, les mécanismes de l'accumulation de GL par des conditions de stress ne sont pas encore bien compris. Notre objectif principal est de comprendre la régulation de la formation de GL par le stress oxydatif, l'inflammation et le stress métabolique. Premièrement, nous avons investigué les GL dans des cellules exposées à des stresseurs tels que des nanocrystaux métalliques et des dérivés réactifs d'oxygène. La formation de GL et l'expression de perilipin-2, qui est une protéine structurelle des GL, ont tous deux augmenté dans les cellules stressées. De plus, une supplémentation en antioxydant (n-acétylcystéine) ou un traitement avec un inhibiteur de p38 MAPK a réduit l'accumulation de GL causée par le stress. Ces observations suggèrent que le stress oxydatif et p38 MAPK jouent un rôle dans l'accumulation de GL dans des cellules stressées. Il est bien connu que les leucocytes et macrophages qui sont engagés dans l'inflammation contiennent une grande quantité de GL. Même si ce phénomène a bien été exploré dans les cellules immunitaires périphériques, il reste inexploré dans le système nerveux central (SNC). Ce faisant, nous avons investigué la dynamique et la régulation des GL dans les microglies, les cellules résidentes immunitaires dans le cerveau. Nous avons trouvé que dans les microglies stimulées avec les lipopolysaccharides (LPS), les GL et l'expression de perilipin-2 ont augmenté d'une manière dépendante de l'activation de l'Akt et p38 MAPK. Dans ces cellules activées, la phospholipase cytosolique A2-α (PLC A2-α), une enzyme fonctionnant dans la synthèse d'éicosanoides, des médiateurs lipidiques inflammatoires, colocalisait avec les GL. Ensemble, ces résultats indiquent que la formation de GL pourrait contribuer à la synthèse d'éicosanoides dans les microglies activées et servir de biomarqueurs d'inflammation dans le SNC.Pour mieux comprendre le rôle des GL dans la pathologie humaine, nous les avons examinées dans des tissues pancréatiques provenant de patients obèses ou diabétiques T2. Nos études immunohistochimiques ont révélé une augmentation de perilipin-2 dans les îlots de Langerhans chez les patients diabétiques obèses ou maigres, mais pas dans ceux de patients non-diabétiques. Ceci suggère que le DT2, mais non l'obésité, est requis pour une augmentation de perilipin-2 dans le pancréas. L'analyse d'expression de gènes par RT-PCR a confirmé l'augmentation de perilipin-2 observé antérieurement dans les îlots et a également révélé des altérations dans des gènes reliés aux fonctions des îlots, au métabolisme, et aux défenses anti-oxydantes. Ces changements, qui sont souvent associés à l'obésité et au DT2, constituent un mécanisme d'adaptation à la résistance à l'insuline et au stress métabolique.Pour résumer, nos études démontrent que l'accumulation de GL fait partie intégrante de l'adaptation des cellules au stress. Durant la prochaine décennie, le plus grand obstacle dans la recherche sur les GL sera de déterminer comment la composition lipidique ou protéinique de ces organites affecte leurs fonctions biologiques.
49
McEwan, S. J. "Studies on skeletal lipid metabolism." Thesis, University of Oxford, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233475.
Full text
50
Deol, Sundeep Singh. "Analysis of lipid-protein interactions." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424760.
Full text