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Lipid raft

Alvaro Toledo, Zhen Huang, Jorge L Benach, Erwin London
Lipid rafts are membrane microdomains that are involved in cellular processes such as protein trafficking and signaling processes, and which play a fundamental role in membrane fluidity and budding. The lipid composition of the membrane and the biochemical characteristics of the lipids found within rafts define the ability of cells to form microdomains and compartmentalize the membrane. In this chapter, we describe the biophysical, biochemical, and molecular approaches used to define and characterize lipid rafts in the Lyme disease agent, Borrelia burgdorferi...
2018: Methods in Molecular Biology
Do-Kyun Kim, Michael A Beaven, Dean D Metcalfe, Ana Olivera
BACKGROUND: DJ-1 is a redox-sensitive protein with multiple roles in cell homeostasis whose levels are altered in mast cell (MC)-related disorders. However, whether DJ-1 can regulate human MC function is unknown. OBJECTIVE: We sought to investigate the potential role of DJ-1 in the responses of human MCs to antigen stimulation. METHODS: DJ-1 was silenced in human CD34(+)-derived and LAD2 MCs using lentiviral sh-RNA constructs. Release of β-hexosaminidase, PGD2 and GM-CSF and changes in reactive oxygen species (ROS) levels were measured after FcεRI engagement...
October 12, 2017: Journal of Allergy and Clinical Immunology
Michael Schick
I consider a model of a bilayer characterized by two order parameters, one in each leaf. That of the inner leaf represents the difference in mol fractions of lipids with large spontaneous curvature, phosphatidylethanolamine, (PE), and those with small spontaneous curvatures, phosphatidylcholine, (PC), and phosphatidylserine, (PS). Similarly the order parameter in the outer leaf represents the difference in mol fractions of lipids with small spontaneous curvature, PC, and large curvature, sphingomyelin, (SM)...
October 12, 2017: Journal of Physical Chemistry. B
Vahideh Rabani, Damien Montange, Nicolas Meneveau, Siamak Davani
Ticagrelor is an antiplatelet agent that inhibits platelet activation via P2Y12 antagonism. There are several studies showing that P2Y12 needs lipid rafts to be activated, but there are few data about how ticagrelor impacts lipid raft organization. Therefore, we aimed to investigate how ticagrelor could impact the distribution of cholesterol and consequently alter the organization of lipid rafts on platelet plasma membranes. We identified cholesterol-enriched raft fractions in platelet membranes by quantification of their cholesterol levels...
October 11, 2017: Platelets
Eric Wang, Jeffery B Klauda
Recent studies in lipid raft formation and stratum corneum permeability have focused on the role of ceramides (CER). In this study, we use the all-atom CHARMM36 (C36) force field to simulate bilayers using N-palmitoyl-sphingosine (CER16) or α-hydroxy-N-stearoyl phytosphingosine (CER[AP]) in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) which serve as general membrane models. Conditions are replicated from experimental studies for comparison purposes, and concentration (XCER) is varied to probe the effect of CER on these systems...
October 10, 2017: Journal of Physical Chemistry. B
Jinhui Wang, Daofei Qu, Jinghong An, Guoming Yuan, Yufu Liu
Glaucoma is characterized as a visual field defect, which is the second most common cause of blindness. The present study performed an integrated analysis of microarray studies of glaucoma derived from Gene Expression Omnibus (GEO). Following the identification of the differentially expressed genes (DEGs) in glaucoma compared with normal control (NC) tissues, the functional annotation, glaucoma‑specific protein‑protein interaction (PPI) network and transcriptional regulatory network constructions were performed...
October 4, 2017: Molecular Medicine Reports
K Gradauer, M Iida, A Watari, M Kataoka, S Yamashita, M Kondoh, S T Buckley
Intestinal permeation enhancers are a crucial component of many oral formulations, without which many drugs would show an insufficient absorption in the gut. The present study sought to provide a better understanding of the molecular interaction of such absorption enhancers with the intestine, by investigating the effect of the surfactant - like permeation enhancer dodecylmaltoside (DDM) on Caco-2 cells. The extent to which the action of DDM is apportioned between the para- and transcellular routes was addressed by examining the transport of relevant marker compounds ([3H]-mannitol and [3H]-propranolol, respectively)...
October 6, 2017: Molecular Pharmaceutics
Junji Egawa, Alice Zemljic-Harpf, Chitra D Mandyam, Ingrid R Niesman, Larisa V Lysenko, Alexander M Kleschevnikov, David M Roth, Hemal H Patel, Piyush M Patel, Brian P Head
A delicate interneuronal communication between pre- and postsynaptic membranes is critical for synaptic plasticity and the formation of memory. Evidence shows that membrane/lipid rafts (MLRs), plasma membrane microdomains enriched in cholesterol and sphingolipids, organize presynaptic proteins and postsynaptic receptors necessary for synaptic formation and signaling. MLRs establish a cell polarity that facilitates transduction of extracellular cues to the intracellular environment. Here we show that neuron-targeted overexpression of an MLR protein, caveolin-1 (SynCav1), in the adult mouse hippocampus increased the number of presynaptic vesicles per bouton, total excitatory type I glutamatergic synapses, number of same-dendrite multiple-synapse boutons, increased myelination, increased long-term potentiation, and increased MLR-localized N-methyl-d-aspartate receptor subunits (GluN1, GluN2A, and GluN2B)...
July 31, 2017: Cerebral Cortex
Helena C Christianson, Julien A Menard, Vineesh Indira Chandran, Erika Bourseau-Guilmain, Dmitry Shevela, Jon Lidfeldt, Ann-Sofie Månsson, Silvia Pastorekova, Johannes Messinger, Mattias Belting
Aggressive cancers are characterized by hypoxia, which is a key driver of tumor development and treatment resistance. Proteins specifically expressed in the hypoxic tumor microenvironment thus represent interesting candidates for targeted drug delivery strategies. Carbonic anhydrase (CAIX) has been identified as an attractive treatment target as it is highly hypoxia specific and expressed at the cell-surface to promote cancer cell aggressiveness. Here, we find that cancer cell internalization of CAIX is negatively regulated by post-translational modification with chondroitin or heparan sulfate glycosaminoglycan chains...
September 15, 2017: Oncotarget
Alessandro Venuta, Francesca Moret, Giovanni Dal Poggetto, Diletta Esposito, Aurore Fraix, Concetta Avitabile, Francesca Ungaro, Mario Malinconico, Salvatore Sortino, Alessandra Romanelli, Paola Laurienzo, Elena Reddi, Fabiana Quaglia
Polymeric nanoparticles (NPs) of poly(ε-caprolactone) (PCL) covered with a hydrophilic poly(ethylene glycol) (PEG) shell are usually prepared from diblock PEG-PCL copolymers through different techniques. Furthermore PEG, NPs can be decorated with targeting ligands to accumulate in specific cell lines. However, the density and conformation of PEG on the surface and its impact on the exposition of small targeting ligands has been poorly considered so far although this has a huge impact on biological behaviour...
September 28, 2017: European Journal of Pharmaceutical Sciences
Eva Laurén, Feven Tigistu-Sahle, Sami Valkonen, Melissa Westberg, Anne Valkeajärvi, Juha Eronen, Pia Siljander, Ville Pettilä, Reijo Käkelä, Saara Laitinen, Erja Kerkelä
Red blood cells (RBCs) are stored up to 35-42days at 2-6°C in blood banks. During storage, the RBC membrane is challenged by energy depletion, decreasing pH, altered cation homeostasis, and oxidative stress, leading to several biochemical and morphological changes in RBCs and to shedding of extracellular vesicles (EVs) into the storage medium. These changes are collectively known as RBC storage lesions. EVs accumulate in stored RBC concentrates and are, thus, transfused into patients. The potency of EVs as bioactive effectors is largely acknowledged, and EVs in RBC concentrates are suspected to mediate some adverse effects of transfusion...
September 28, 2017: Biochimica et Biophysica Acta
Yong Zhang, Hong Liu, Wei Li, Zhengang Zhang, Xuejun Shang, David Zhang, Yuhong Li, Shiyang Zhang, Junpin Liu, Rex A Hess, Gregory J Pazour, Zhibing Zhang
Intraflagellar transport (IFT) is an evolutionarily conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. In mice, mutations in IFT proteins have been shown to cause several ciliopathies including retinal degeneration, polycystic kidney disease, and hearing loss. However, little is known about its role in the formation of the sperm tail, which has the longest flagella of mammalian cells. IFT27 is a component of IFT-B complex and binds to IFT25 directly. In mice, IFT27 is highly expressed in the testis...
September 27, 2017: Developmental Biology
Chetasi Talati, David Sallman, Alan List
Myelodysplastic syndrome (MDS) with deletion 5q (del(5q)) is a distinct clinical and pathological disease subset that is exquisitely sensitive to lenalidomide for the treatment of red blood cell transfusion-dependent anemia. Although lenalidomide has erythropoeitic promoting activity in MDS without del(5q) (non-del(5q) MDS), the frequency of response to treatment is lower and relates to biologically separate drug effects. In del(5q) MDS, lenalidomide suppresses the malignant clone to restore effective erythropoiesis by virtue of synthetic lethality, arising from cereblon-dependent degradation of haplodeficient proteins encoded within the commonly deleted region of the chromosome 5q deletion...
July 2017: Seminars in Hematology
Ivanildo P Sousa, Carlos A Marques Carvalho, Ygara Silva Mendes, Gilberto Weissmuller, Andréa C Oliveira, Andre M O Gomes
Alphaviruses are enveloped arboviruses mainly proposed to infect host cells by receptor-mediated endocytosis followed by fusion between the viral envelope and the endosomal membrane. The fusion reaction is triggered by low pH and requires the presence of both cholesterol and sphingolipids in the target membrane, suggesting the involvement of lipid rafts in the cell entry mechanism. In this study, we show for the first time the interaction of an enveloped virus with membrane microdomains isolated from living cells...
September 28, 2017: Biochemistry
Marco Diociaiuti, Cristiano Giordani, Gihan S Kamel, Francesco Brasili, Simona Sennato, Cecilia Bombelli, Karen Y Meneses, Marco A Giraldo, Federico Bordi
GM1 ganglioside is known to be involved in the amyloid-associated diseases and it is a crucial factor for the assembly of amyloid proteins on lipid-rafts, which are lipid structures located on the synaptic plasma membranes. Due to its slow aggregation rate, we employed salmon calcitonin (sCT) as a suitable probe representative of amyloid proteins, to study the interaction between this class of proteins and a membrane model. Here, we prepared a neuronal membrane model by depositing onto mica two Langmuir-Blodgett films in liquid-condensed phase: the outer monolayer was characterized by high content of GM1 (50%) and minority parts of cholesterol and POPC (25-25%), while the inner one by plain POPC...
December 2016: Biochemistry and Biophysics Reports
Joshua F Ceñido, Boris Itin, Ruth E Stark, Yung-Yu Huang, Maria A Oquendo, J John Mann, M Elizabeth Sublette
Lipid microdomains ('lipid rafts') are plasma membrane subregions, enriched in cholesterol and glycosphingolipids, which participate dynamically in cell signaling and molecular trafficking operations. One strategy for the study of the physicochemical properties of lipid rafts in model membrane systems has been the use of nuclear magnetic resonance (NMR), but until now this spectroscopic method has not been considered a clinically relevant tool. We performed a proof-of-concept study to test the feasibility of using NMR to study lipid rafts in human tissues...
July 2017: Biochemistry and Biophysics Reports
Robin S B Williams, Clive Bate
The amyloid hypothesis of Alzheimer's disease suggests that synaptic degeneration and pathology is caused by the accumulation of amyloid-β (Aβ) peptides derived from the amyloid precursor protein (APP). Subsequently, soluble Aβ oligomers cause the loss of synaptic proteins from neurons, a histopathological feature of Alzheimer's disease that correlates with the degree of dementia. In this study, the production of toxic forms of Aβ was examined in vitro using 7PA2 cells stably transfected with human APP...
September 22, 2017: Neuropharmacology
Lukas J Patalag, Jeremias Sibold, Ole M Schütte, Claudia Steinem, Daniel B Werz
Glycosphingolipids are involved in a number of physiological and pathophysiological processes, and they serve as receptors for a variety of bacterial toxins and viruses. To investigate their function in lipid membranes, fluorescently labeled glycosphingolipids are highly desirable. Herein, a synthetic route to access Gb3 glycosphingolipids with fluorescently labeled fatty acids, consisting of pentaene and hexaene moieties either at the terminus or in the middle of the acyl chain, has been developed. The fluorescent properties of the Gb3 derivatives were investigated in small unilamellar vesicles composed of a raft-like mixture...
September 20, 2017: Chembiochem: a European Journal of Chemical Biology
Leonardo Ermini, Jonathan Ausman, Megan Melland-Smith, Behzad Yeganeh, Alessandro Rolfo, Michael L Litvack, Tullia Todros, Michelle Letarte, Martin Post, Isabella Caniggia
Preeclampsia (PE), an hypertensive disorder of pregnancy, exhibits increased circulating levels of a short form of the auxillary TGF-beta (TGFB) receptor endoglin (sENG). Until now, its release and functionality in PE remains poorly understood. Here we show that ENG selectively interacts with sphingomyelin(SM)-18:0 which promotes its clustering with metalloproteinase 14 (MMP14) in SM-18:0 enriched lipid rafts of the apical syncytial membranes from PE placenta where ENG is cleaved by MMP14 into sENG. The SM-18:0 enriched lipid rafts also contain type 1 and 2 TGFB receptors (TGFBR1 and TGFBR2), but not soluble fms-like tyrosine kinase 1 (sFLT1), another protein secreted in excess in the circulation of women with PE...
September 22, 2017: Scientific Reports
Anton A A Smith, Henriette Elisabeth Autzen, Tomas Laursen, Vincent Wu, Max Yen, Aaron Hall, Scott D Hansen, Yifan Cheng, Ting Xu
The ability of styrene maleic acid copolymers to dissolve lipid membranes into nanosized lipid particles is a facile method of obtaining membrane proteins in solubilized lipid discs while conserving part of its native lipid environment. While the currently used copolymers can readily extract membrane proteins in native nanodiscs, their highly disperse composition is likely to influence the dispersity of the discs as well as the extraction efficiency. In this study, reversible addition fragmentation chain transfer was used to control the polymer architecture and dispersity of molecular weights with a high-precision...
September 21, 2017: Biomacromolecules
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