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Sphingomyelin

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https://www.readbyqxmd.com/read/29772704/lateral-membrane-heterogeneity-regulates-viral-induced-membrane-fusion-during-hiv-entry
#1
Rodion J Molotkovsky, Veronika V Alexandrova, Timur R Galimzyanov, Irene Jiménez-Munguía, Konstantin V Pavlov, Oleg V Batishchev, Sergey A Akimov
Sphingomyelin- and cholesterol- enriched membrane domains, commonly referred to as "rafts" play a crucial role in a large number of intra- and intercellular processes. Recent experiments suggest that not only the volumetric inhomogeneity of lipid distribution in rafts, but also the arrangement of the 1D boundary between the raft and the surrounding membrane is important for the membrane-associated processes. The reason is that the boundary preferentially recruits different peptides, such as HIV (human immunodeficiency virus) fusion peptide...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29769046/%C3%AE-tocotrienol-induces-apoptosis-in-pancreatic-cancer-cells-by-upregulation-of-ceramide-synthesis-and-modulation-of-sphingolipid-transport
#2
Victoria E Palau, Kanishka Chakraborty, Daniel Wann, Janet Lightner, Keely Hilton, Marianne Brannon, William Stone, Koyamangalath Krishnan
BACKGROUND: Ceramide synthesis and metabolism is a promising target in cancer drug development. γ-tocotrienol (GT3), a member of the vitamin E family, orchestrates multiple effects that ensure the induction of apoptosis in both, wild-type and RAS-mutated pancreatic cancer cells. Here, we investigated whether these effects involve changes in ceramide synthesis and transport. METHODS: The effects of GT3 on the synthesis of ceramide via the de novo pathway, and the hydrolysis of sphingomyelin were analyzed by the expression levels of the enzymes serine palmitoyl transferase, ceramide synthase-6, and dihydroceramide desaturase, and acid sphingomyelinase in wild-type RAS BxPC3, and RAS-mutated MIA PaCa-2 and Panc 1 pancreatic cancer cells...
May 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29766830/impact-of-sphingolipid-mediators-on-determination-of-cochlear-survival-in-ototoxicity
#3
Keiji Tabuchi, Akira Hara
BACKGROUND AND OBJECTIVE: Sphingolipid metabolites, including ceramide, sphingosine, and their phosphorylates (ceramide-1-phosphonate [C1P] and sphingosine-1-phosphate [S1P]), regulate diverse cellular processes including apoptosis, the cell cycle, and cellular differentiation. Recent studies have shown that these sphingolipid metabolites are generated in response to ototoxic agents and play important roles in determining the fate of cochlear hair cells in ototoxic injury. METHODS: This review summarizes the current knowledge on the roles of sphingolipid mediators in cochlear ototoxicity...
May 15, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29760920/serum-lipidomics-of-bovine-paratuberculosis-disruption-of-choline-containing-glycerophospholipids-and-sphingolipids
#4
Paul L Wood, Erdal Erol, Glen F Hoffsis, Margaret Steinman, Jeroen DeBuck
Objectives: Bovine paratuberculosis is a devastating infection with Mycobacterium avium subspecies paratuberculosis that ultimately results in death from malnutrition. While the infection is characterized by a long (2-4 years) subclinical phase with immune activation, ultimately host defense mechanisms fail and the bacteria spread from the small intestine to other organs. Since both the gastrointestinal tract and liver are essential for the biosynthesis of structural glycerophospholipids, we investigated the circulating levels of these lipids in field infections and experimentally infected cattle...
2018: SAGE Open Medicine
https://www.readbyqxmd.com/read/29754486/nanoparticle-wettability-influences-nanoparticle-phospholipid-interactions
#5
Nagarjun Konduru, Flavia Damiani, Svetla Stoilova-McPhie, Jason Tresback, Georgios Pyrgiotakis, Thomas C Donaghey, Philip Demokritou, Joseph Brain, Ramon M Molina
We explored the influence of nanoparticle (NP) surface charge and hydrophobicity on nanoparticle-biomolecule interactions by measuring the composition of adsorbed phospholipids on four NPs, namely positively charged CeO2 and ZnO, and negatively charged BaSO4 and silica-coated CeO2 after exposure to bronchoalveolar lavage fluid (BALf) obtained from rats, and to a mixture of neutral dipalmitoyl phosphatidylcholine (DPPC) and negatively charged dipalmitoyl phosphatidic acid (DPPA). The resulting NP-lipid interactions were examined by cryogenic transmission electron microscopy (cryo-TEM) and by atomic force microscopy (AFM)...
May 12, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29753650/sphingomyelin-ability-to-act-as-chiral-selector-using-nanodisc-electrokinetic-chromatography
#6
William M Penny, Christopher P Palmer
Understanding how stereochemistry affects interactions with cell membranes is important for effective drug development. Chirality has been shown to greatly effect pharmaceutical distribution and metabolism within the cell. However it has been thought that interactions with, and passive diffusion through, the membrane are not stereochemically selective. Various studies have produced conflicting results regarding whether interactions with lipid bilayers are or can be stereoselective. In the current work, stereoselective interactions between a pair of atropisomers, R-(+)/(S)-(-) 1,1'-Bi-2-naphthol, and sphingomyelin nanodisc bilayers, are demonstrated...
May 10, 2018: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/29748690/untargeted-lipidomic-analysis-of-primary-human-epidermal-melanocytes-acutely-and-chronically-exposed-to-uv-radiation
#7
Núria Dalmau, Nathalie Andrieu-Abadie, Romà Tauler, Carmen Bedia
Ultraviolet (UV) radiation present in sunlight has been related to harmful effects on skin such as premature aging and skin cancer. In order to study the effects of UV radiation on skin, many investigations have been carried out at transcriptomic and proteomic levels. However, studies on the effects of UV radiation on lipid composition are scarce. In this work, primary cultures of melanocytes were exposed to UV radiation in a similar UVA/UVB ratio to that found in solar light. The UV exposure was carried out twice a week and different endpoints were investigated at 0...
May 11, 2018: Molecular omics
https://www.readbyqxmd.com/read/29746165/a-lysosome-plasma-membrane-sphingolipid-axis-linking-lysosomal-storage-to-cell-growth-arrest
#8
Maura Samarani, Nicoletta Loberto, Giulia Soldà, Letizia Straniero, Rosanna Asselta, Stefano Duga, Giulia Lunghi, Fabio A Zucca, Laura Mauri, Maria Grazia Ciampa, Domitilla Schiumarini, Rosaria Bassi, Paola Giussani, Elena Chiricozzi, Alessandro Prinetti, Massimo Aureli, Sandro Sonnino
Lysosomal accumulation of undegraded materials is a common feature of lysosomal storage diseases, neurodegenerative disorders, and the aging process. To better understand the role of lysosomal storage in the onset of cell damage, we used human fibroblasts loaded with sucrose as a model of lysosomal accumulation. Sucrose-loaded fibroblasts displayed increased lysosomal biogenesis followed by arrested cell proliferation. Notably, we found that reduced lysosomal catabolism and autophagy impairment led to an increase in sphingolipids ( i...
May 10, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29742408/membrane-bending-moduli-of-coexisting-liquid-phases-containing-transmembrane-peptide
#9
Rebecca D Usery, Thais A Enoki, Sanjula P Wickramasinghe, V P Nguyen, David G Ackerman, Denise V Greathouse, Roger E Koeppe, Francisco N Barrera, Gerald W Feigenson
A number of highly curved membranes in vivo, such as epithelial cell microvilli, have the relatively high sphingolipid content associated with "raft-like" composition. Given the much lower bending energy measured for bilayers with "nonraft" low sphingomyelin and low cholesterol content, observing high curvature for presumably more rigid compositions seems counterintuitive. To understand this behavior, we measured membrane rigidity by fluctuation analysis of giant unilamellar vesicles. We found that including a transmembrane helical GWALP peptide increases the membrane bending modulus of the liquid-disordered (Ld) phase...
May 8, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29738703/high-fat-diet-induced-obesity-is-mitigated-in-cyp3a-null-female-mice
#10
Ramiya Kumar, Elizabeth J Litoff, W Tyler Boswell, William S Baldwin
Recent studies indicate a role for the constitutive androstane receptor (CAR), pregnane X-receptor (PXR), and hepatic xenobiotic detoxifying CYPs in fatty liver disease or obesity. Therefore, we examined whether Cyp3a-null mice show increased obesity and fatty liver disease following 8-weeks of exposure to a 60% high-fat diet (HFD). Surprisingly, HFD-fed Cyp3a-null females fed a HFD gained 50% less weight than wild-type (WT; B6) females fed a HFD. In contrast, Cyp3a-null males gained more weight than WT males, primarily during the first few weeks of HFD-treatment...
May 5, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29738550/genome-wide-association-meta-analysis-of-circulating-odd-numbered-chain-saturated-fatty-acids-results-from-the-charge-consortium
#11
Marcia C de Oliveira Otto, Rozenn N Lemaitre, Qi Sun, Irena B King, Jason H Y Wu, Ani Manichaikul, Stephen S Rich, Michael Y Tsai, Y D Chen, Myriam Fornage, Guan Weihua, Stella Aslibekyan, Marguerite R Irvin, Edmond K Kabagambe, Donna K Arnett, Majken K Jensen, Barbara McKnight, Bruce M Psaty, Lyn M Steffen, Caren E Smith, Ulf Risérus, Lars Lind, Frank B Hu, Eric B Rimm, David S Siscovick, Dariush Mozaffarian
BACKGROUND: Odd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Although some OCSFA (e.g., C15:0 and C17:0) are found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are relatively unknown, and the influence of non-dietary determinants, including genetic factors, on circulating levels of OCSFA is not established. OBJECTIVE: To elucidate the biological processes that influence circulating levels of OCSFA by investigating associations between genetic variation and OCSFA...
2018: PloS One
https://www.readbyqxmd.com/read/29737914/lipidomics-reveal-aryl-hydrocarbon-receptor-ahr-regulated-lipid-metabolic-pathway-in-alpha-naphthyl-isothiocyanate-anit-induced-intrahepatic-cholestasis
#12
Bao-Long Wang, Chang-Wen Zhang, Liang Wang, Kun-Long Tang, Naoki Tanaka, Frank J Gonzalez, Yong Xu, Zhong-Ze Fang
1. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based lipidomics was employ to elucidate new mechanism of alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. 2. Multiple lipid components significantly increased in ANIT-induced intrahepatic cholestasis, including PC 16:0, 20:4, PC 16:0, 22:6, PC 16:0, 18:2, LPC 18:2, PC 18:2, LPC 18:1, PC 18:1, 14:0, SM 18:1, 16:0, oleoylcarnitine, and palmitoylcarnitine...
May 8, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29737333/multimodal-imaging-of-undecalcified-tissue-sections-by-maldi-ms-and-%C3%AE-xrf
#13
Anastasiya Svirkova, Anna Turyanskaya, Lukas Perneczky, Christina Streli, Martina Marchetti-Deschmann
Matrix-assisted laser desorption/ionisation mass spectrometric imaging (MALDI MSI) is a technique that provides localized information on intact molecules in a sample. Micro X-ray fluorescence (μXRF) imaging allows the examination of the spatial distribution of elements in a sample without any morphological changes. These methods have already been applied separately to different tissues, organs, plants and bacterial films, but, to the best of our knowledge, they have yet to be coupled in a multimodal analysis...
May 8, 2018: Analyst
https://www.readbyqxmd.com/read/29730243/docosahexaenoic-acid-regulates-the-formation-of-lipid-rafts-a-unified-view-from-experiment-and-simulation
#14
Stephen R Wassall, Xiaoling Leng, Samuel W Canner, Edward Ross Pennington, Jacob J Kinnun, Andres T Cavazos, Sahil Dadoo, Dylan Johnson, Frederick A Heberle, John Katsaras, Saame Raza Shaikh
Docosahexaenoic acid (DHA, 22:6) is an n-3 polyunsaturated fatty acid (n-3 PUFA) that influences immunological, metabolic, and neurological responses through complex mechanisms. One structural mechanism by which DHA exerts its biological effects is through its ability to modify the physical organization of plasma membrane signaling assemblies known as sphingomyelin/cholesterol (SM/chol)-enriched lipid rafts. Here we studied how DHA acyl chains esterified in the sn-2 position of phosphatidylcholine (PC) regulate the formation of raft and non-raft domains in mixtures with SM and chol on differing size scales...
May 3, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29725009/smpd3-deficiency-perturbs-neuronal-proteostasis-and-causes-progressive-cognitive-impairment
#15
Wilhelm Stoffel, Britta Jenke, Inga Schmidt-Soltau, Erika Binczek, Susanne Brodesser, Ina Hammels
Neutral sphingomyelinase smpd3 is most abundantly expressed in neurons of brain. The function of SMPD3 has remained elusive. Here, we report a pathogenetic nexus between absence of SMPD3 in the Golgi compartment (GC) of neurons of the smpd3-/- mouse brain, inhibition of Golgi vesicular protein transport and progressive cognitive impairment. Absence of SMPD3 activity in the Golgi sphingomyelin cycle impedes remodeling of the lipid bilayer, essential for budding and multivesicular body formation. Importantly, we show that inhibition of the Golgi vesicular protein transport causes accumulation of neurotoxic proteins APP, Aβ and phosphorylated Tau, dysproteostasis, unfolded protein response, and apoptosis, which ultimately manifests in progressive cognitive decline, similar to the pathognomonic signatures of familial and sporadic forms of Alzheimer´s disease...
May 3, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29724781/identification-of-an-acid-sphingomyelinase-ceramide-kinase-pathway-in-the-regulation-of-the-chemokine-ccl5
#16
Benjamin Newcomb, Cosima Rhein, Izolda Mileva, Rasheed Ahmad, Christopher J Clarke, Justin Snider, Lina M Obeid, Yusuf A Hannun
Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to produce the biologically active lipid ceramide. Previous studies have implicated ASM in the induction of the chemokine CCL5 in response to TNF-α, however, the lipid mediator of this effect was not established. In the present study, we identified a novel pathway connecting ASM and ceramide kinase (CERK). The results show that TNF-α induces the formation of ceramide 1-phosphate (C-1-P) in a CERK-dependent manner. Silencing of CERK blocks CCL5 production in response to TNF-α...
May 3, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29720382/adherens-junctions-influence-tight-junction-formation-via-changes-in-membrane-lipid-composition
#17
Kenta Shigetomi, Yumiko Ono, Tetsuichiro Inai, Junichi Ikenouchi
Tight junctions (TJs) are essential cell adhesion structures that act as a barrier to separate the internal milieu from the external environment in multicellular organisms. Although their major constituents have been identified, it is unknown how the formation of TJs is regulated. TJ formation depends on the preceding formation of adherens junctions (AJs) in epithelial cells; however, the underlying mechanism remains to be elucidated. In this study, loss of AJs in α-catenin-knockout (KO) EpH4 epithelial cells altered the lipid composition of the plasma membrane (PM) and led to endocytosis of claudins, a major component of TJs...
May 2, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29720183/disrupted-sphingolipid-metabolism-following-acute-clozapine-and-olanzapine-administration
#18
Katrina Weston-Green, Ilijana Babic, Michael de Santis, Bo Pan, Magdalene K Montgomery, Todd Mitchell, Xu-Feng Huang, Jessica Nealon
BACKGROUND: Second generation antipsychotics (SGAs) induce glucometabolic side-effects, such as hyperglycemia and insulin resistance, which pose a therapeutic challenge for mental illness. Sphingolipids play a role in glycaemic balance and insulin resistance. Endoplasmic reticulum (ER) stress contributes to impaired insulin signalling and whole-body glucose intolerance. Diabetogenic SGA effects on ER stress and sphingolipids, such as ceramide and sphingomyelin, in peripheral metabolic tissues are unknown...
May 2, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29718662/high-spatial-resolution-imaging-of-mouse-pancreatic-islets-using-nanospray-desorption-electrospray-ionization-mass-spectrometry
#19
Ruichuan Yin, Jennifer E Kyle, Kristin E Burnum-Johnson, Kent Bloodsworth, Lori Sussel, Charles Ansong, Julia Laskin
Nanospray Desorption Electrospray Ionization mass spectrometry imaging (nano-DESI MSI) enables ambient imaging of biological samples with high sensitivity and minimal sample pretreatment. Recently, we developed an approach for constant-distance mode MSI using shear force microscopy to precisely control the distance between the sample and the nano-DESI probe. Herein, we demonstrate the power of this approach for robust imaging of pancreatic islets with high spatial resolution of ~11 μm. Pancreatic islets are difficult to characterize using traditional mass spectrometry approaches due to their small size (~100 μm) and molecular heterogeneity...
May 2, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29716234/impact-of-amphiphilic-molecules-on-the-structure-and-stability-of-homogeneous-sphingomyelin-bilayer-insights-from-atomistic-simulations
#20
Pratibha Kumari, Supreet Kaur, Shobha Sharma, Hemant K Kashyap
Modulation of lipid membrane properties due to the permeation of amphiphiles is an important biological process pertaining to many applications in the field of pharmaceutics, toxicology, and biotechnology. Sphingolipids are both structural and functional lipids that constitute an important component of mechanically stable and chemically resistant outer leaflets of plasma membranes. Here, we present an atomistic molecular dynamics simulation study to appreciate the concentration-dependent effects of small amphiphilic molecules, such as ethanol, acetone, and dimethyl sulfoxide (DMSO), on the structure and stability of a fully hydrated homogeneous N-palmitoyl-sphingomyelin (PSM) bilayer...
April 28, 2018: Journal of Chemical Physics
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