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Plasma membrane ceramide

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https://www.readbyqxmd.com/read/28468968/tolerogenic-versus-immunogenic-lipidomic-profiles-of-cd11c-immune-cells-and-control-of-immunogenic-dendritic-cell-ceramide-dynamics
#1
Carlos Ocaña-Morgner, Susanne Sales, Manuela Rothe, Andrej Shevchenko, Rolf Jessberger
Lipids affect the membrane properties determining essential biological processes. Earlier studies have suggested a role of switch-activated protein 70 (SWAP-70) in lipid raft formation of dendritic cells. We used lipidomics combined with genetic and biochemical assays to analyze the role of SWAP-70 in lipid dynamics. TLR activation using LPS as a ligand represented a pathogenic immunogenic stimulus, physical disruption of cell-cell contacts a tolerogenic stimulus. Physical disruption, but not LPS, caused an increase of phosphatidylcholine ether and cholesteryl esters in CD11c(+) immune cells...
May 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28411183/membrane-permeation-of-arginine-rich-cell-penetrating-peptides-independent-of-transmembrane-potential-as-a-function-of-lipid-composition-and-membrane-fluidity
#2
Rike Wallbrecher, Tobias Ackels, R Alis Olea, Marco J Klein, Lucie Caillon, Jürgen Schiller, Petra H Bovée-Geurts, Toin H van Kuppevelt, Anne S Ulrich, Marc Spehr, Merel J W Adjobo-Hermans, Roland Brock
Cell-penetrating peptides (CPPs) are prominent delivery vehicles to confer cellular entry of (bio-) macromolecules. Internalization efficiency and uptake mechanism depend, next to the type of CPP and cargo, also on cell type. Direct penetration of the plasma membrane is the preferred route of entry as this circumvents endolysosomal sequestration. However, the molecular parameters underlying this import mechanism are still poorly defined. Here, we make use of the frequently used HeLa and HEK cell lines to address the role of lipid composition and membrane potential...
April 12, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28409208/inhibitors-of-ceramide-de-novo-biosynthesis-rescue-damages-induced-by-cigarette-smoke-in-airways-epithelia
#3
Aida Zulueta, Anna Caretti, Giuseppe Matteo Campisi, Andrea Brizzolari, Jose Luis Abad, Rita Paroni, Paola Signorelli, Riccardo Ghidoni
Exposure to cigarette smoke represents the most important risk factor for the development of chronic obstructive pulmonary disease (COPD). COPD is characterized by chronic inflammation of the airways, imbalance of proteolytic activity resulting in the destruction of lung parenchyma, alveolar hypoxia, oxidative stress, and apoptosis. Sphingolipids are structural membrane components whose metabolism is altered during stress. Known as apoptosis and inflammation inducer, the sphingolipid ceramide was found to accumulate in COPD airways and its plasma concentration increased as well...
April 13, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28405720/ceramide-synthase-2-deficiency-aggravates-aom-dss-induced-colitis-in-mice-role-of-colon-barrier-integrity
#4
Stephanie Oertel, Klaus Scholich, Andreas Weigert, Dominique Thomas, Julia Schmetzer, Sandra Trautmann, Marthe-Susanna Wegner, Heinfried H Radeke, Natalie Filmann, Bernhard Brüne, Gerd Geisslinger, Irmgard Tegeder, Sabine Grösch
Loss of intestinal barrier functions is a hallmark of inflammatory bowel disease like ulcerative colitis. The molecular mechanisms are not well understood, but likely involve dysregulation of membrane composition, fluidity, and permeability, which are all essentially regulated by sphingolipids, including ceramides of different chain length and saturation. Here, we used a loss-of-function model (CerS2(+/+) and CerS2(-/-) mice) to investigate the impact of ceramide synthase 2, a key enzyme in the generation of very long-chain ceramides, in the dextran sodium salt (DSS) evoked model of UC...
April 12, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28379629/characterization-of-plasma-membrane-ceramides-by-super-resolution-microscopy
#5
Anne Burgert, Jan Schlegel, Jérôme Bécam, Sören Doose, Erhard Bieberich, Alexandra Schubert-Unkmeir, Markus Sauer
The sphingolipid ceramide regulates cellular processes such as differentiation, proliferation, growth arrest, and apoptosis. Ceramide-rich membrane areas promote structural changes within the plasma membrane that segregate membrane receptors and affect membrane curvature and vesicle formation, fusion, and trafficking. Ceramides were labeled by immunocytochemistry to visualize their distribution on the plasma membrane of different cells with virtually molecular resolution by direct stochastic optical reconstruction microscopy (dSTORM)...
April 5, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28336574/switching-head-group-selectivity-in-mammalian-sphingolipid-biosynthesis-by-active-site-engineering-of-sphingomyelin-synthases
#6
Matthijs Kol, Radhakrishnan Panatala, Mirjana Nordmann, Leoni Swart, Leonie van Suijlekom, Birol Cabukusta, Angelika Hilderink, Tanja Grabietz, John G M Mina, Pentti Somerharju, Sergei Korneev, Fikadu G Tafesse, Joost C M Holthuis
SM is a fundamental component of mammalian cell membranes that contributes to mechanical stability, signaling, and sorting. Its production involves the transfer of phosphocholine from phosphatidylcholine onto ceramide, a reaction catalyzed by SM synthase (SMS)1 in the Golgi and SMS2 at the plasma membrane. Mammalian cells also synthesize trace amounts of the SM analog, ceramide phosphoethanolamine (CPE), but the physiological relevance of CPE production is unclear. Previous work revealed that SMS2 is a bifunctional enzyme producing both SM and CPE, whereas a closely related enzyme, SMS-related protein (SMSr)/SAMD8, acts as a monofunctional CPE synthase in the endoplasmic reticulum...
May 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28275055/altered-expression-of-ganglioside-gm3-molecular-species-and-a-potential-regulatory-role-during-myoblast-differentiation
#7
Shinji Go, Shiori Go, Lucas Veillon, Maria Grazia Ciampa, Laura Mauri, Chihiro Sato, Ken Kitajima, Alessandro Prinetti, Sandro Sonnino, Jin-Ichi Inokuchi
Gangliosides (sialic acid-containing glycosphingolipids) help regulate many important biological processes, including cell proliferation, signal transduction, and differentiation, via formation of functional microdomains in plasma membranes. The structural diversity of gangliosides arises from both the ceramide moiety and glycan portion. Recently, differing molecular species of a given ganglioside are suggested to have distinct biological properties and regulate specific and distinct biological events. Elucidation of the function of each molecular species is important and will provide new insights into ganglioside biology...
April 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28238856/gemcitabine-kills-proliferating-endothelial-cells-exclusively-via-acid-sphingomyelinase-activation
#8
Albert J van Hell, Adriana Haimovitz-Friedman, Zvi Fuks, William D Tap, Richard Kolesnick
Gemcitabine is a widely-used anti-cancer drug with a well-defined mechanism of action in normal and transformed epithelial cells. However, its effect on endothelial cells is largely unknown. Acid sphingomyelinase (ASMase) is highly expressed in endothelial cells, converting plasma membrane sphingomyelin to pro-apoptotic ceramide upon activation by diverse stresses. In the current study, we investigated gemcitabine impact in primary cultures of endothelial cells. We find baseline ASMase increases markedly in bovine aortic endothelial cells (BAEC) as they transit from a proliferative to a confluent growth-arrested state...
February 24, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28223543/role-of-caspases-in-cd95-induced-biphasic-activation-of-acid-sphingomyelinase
#9
Mario Stephan, Bärbel Edelmann, Supandi Winoto-Morbach, Ottmar Janssen, Uwe Bertsch, Cristiana Perrotta, Stefan Schütze, Jürgen Fritsch
Acid sphingomyelinase (A-SMase) plays an important role in the initiation of CD95 signaling by forming ceramide-enriched membrane domains that enable clustering and activation of the death receptors. In TNF-R1 and TRAIL-R1/R2 signaling, A-SMase also contributes to the lysosomal apoptosis pathway triggered by receptor internalization. Here, we investigated the molecular mechanism of CD95-mediated A-SMase activation, demonstrating that A-SMase is located in internalized CD95-receptosomes and is activated by the CD95/CD95L complex in a biphasic manner...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28214863/stimulation-of-erythrocyte-cell-membrane-scrambling-by-c-reactive-protein
#10
Majed Abed, Christian Thiel, Syeda T Towhid, Kousi Alzoubi, Sabina Honisch, Florian Lang, Alfred Königsrainer
BACKGROUND: Eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phosphatidylserine-translocation, is triggered by fever and inflammation. Signaling includes increased cytosolic Ca2+-activity ([Ca2+]i), caspase activation, and ceramide. Inflammation is associated with increased plasma concentration of C-reactive protein (CRP). The present study explored whether CRP triggers eryptosis. METHODS: Phosphatidylserine abundance at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ceramide abundance and caspase-3-activity utilizing FITC-conjugated antibodies...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28179144/plasma-membrane-reorganization-links-acid-sphingomyelinase-ceramide-to-p38-mapk-pathways-in-endothelial-cells-apoptosis
#11
Colin Niaudet, Stéphanie Bonnaud, Maëva Guillonneau, Sébastien Gouard, Marie-Hélène Gaugler, Soizic Dutoit, Natacha Ripoche, Nolwenn Dubois, Valérie Trichet, Isabelle Corre, François Paris
The p38 MAPK signaling pathway is essential in the cellular response to stress stimuli, in particular in the endothelial cells that are major target of external stress. The importance of the bioactive sphingolipid ceramide generated by acid sphingomyelinase is also firmly established in stress-induced endothelial apoptotic cell death. Despite a suggested link between the p38 MAPK and ceramide pathways, the exact molecular events of this connection remain elusive. In the present study, by using two different activators of p38 MAPK, namely anisomycin and ionizing radiation, we depicted how ceramide generated by acid sphingomyelinase was involved in p38 MAPK-dependent apoptosis of endothelial cells...
February 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28120887/er-residency-of-the-ceramide-phosphoethanolamine-synthase-smsr-relies-on-homotypic-oligomerization-mediated-by-its-sam-domain
#12
Birol Cabukusta, Matthijs Kol, Laura Kneller, Angelika Hilderink, Andreas Bickert, John G M Mina, Sergei Korneev, Joost C M Holthuis
SMSr/SAMD8 is an ER-resident ceramide phosphoethanolamine synthase with a critical role in controlling ER ceramides and suppressing ceramide-induced apoptosis in cultured cells. SMSr-mediated ceramide homeostasis relies on the enzyme's catalytic activity as well as on its N-terminal sterile α-motif or SAM domain. Here we report that SMSr-SAM is structurally and functionally related to the SAM domain of diacylglycerol kinase DGKδ, a central regulator of lipid signaling at the plasma membrane. Native gel electrophoresis indicates that both SAM domains form homotypic oligomers...
January 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28104532/sphingolipids-and-glycerophospholipids-the-ying-and-yang-of-lipotoxicity-in-metabolic-diseases
#13
REVIEW
S Rodriguez-Cuenca, V Pellegrinelli, M Campbell, M Oresic, A Vidal-Puig
Sphingolipids in general and ceramides in particular, contribute to pathophysiological mechanisms by modifying signalling and metabolic pathways. Here, we present the available evidence for a bidirectional homeostatic crosstalk between sphingolipids and glycerophospholipids, whose dysregulation contributes to lipotoxicity induced metabolic stress. The initial evidence for this crosstalk originates from simulated models designed to investigate the biophysical properties of sphingolipids in plasma membrane representations...
April 2017: Progress in Lipid Research
https://www.readbyqxmd.com/read/28078595/method-to-measure-sphingomyelin-synthase-activity-changes-in-response-to-cd95l
#14
Fatima Bilal, Michaël Pérès, Nathalie Andrieu-Abadie, Thierry Levade, Bassam Badran, Ahmad Daher, Bruno Ségui
Sphingomyelin synthases 1 and 2 convert the anti-oncometabolite ceramide to sphingomyelin, the most abundant sphingolipid in plasma membrane. CD95L-induced ceramide increase is associated with the caspase-dependent inhibition of sphingomyelin synthesis, which enhances the mitochondrial route to apoptosis. Knocking down sphingomyelin synthase 1 or inhibiting sphingomyelin synthesis facilitates ceramide accumulation, cytochrome c release from mitochondria, and caspase-9 activation in cancer cell upon CD95L treatment...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28019031/pathogen-inactivation-by-riboflavin-and-ultraviolet-light-illumination-accelerates-the-red-blood-cell-storage-lesion-and-promotes-eryptosis
#15
Syed M Qadri, Deborah Chen, Peter Schubert, Darian L Perruzza, Varsha Bhakta, Dana V Devine, William P Sheffield
BACKGROUND: Pathogen reduction treatment using riboflavin and ultraviolet light illumination (Mirasol) effectively reduces the risk of transfusion-transmitted infections. This treatment is currently licensed for only platelets and plasma products, while its application to whole blood (WB) to generate pathogen-inactivated red blood cells (RBCs) is under development. RBC storage lesion, constituting numerous morphologic and biochemical changes, influences RBC quality and limits shelf life...
March 2017: Transfusion
https://www.readbyqxmd.com/read/27872481/imaging-cellular-dynamics-with-spectral-relaxation-imaging-microscopy-distinct-spectral-dynamics-in-golgi-membranes-of-living-cells
#16
Alireza Lajevardipour, James W M Chon, Amitabha Chattopadhyay, Andrew H A Clayton
Spectral relaxation from fluorescent probes is a useful technique for determining the dynamics of condensed phases. To this end, we have developed a method based on wide-field spectral fluorescence lifetime imaging microscopy to extract spectral relaxation correlation times of fluorescent probes in living cells. We show that measurement of the phase and modulation of fluorescence from two wavelengths permit the identification and determination of excited state lifetimes and spectral relaxation correlation times at a single modulation frequency...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27836988/sphingomyelinase-like-phosphodiesterase-3b-mediates-radiation-induced-damage-of-renal-podocytes
#17
Anis Ahmad, Alla Mitrofanova, Jacek Bielawski, Yidong Yang, Brian Marples, Alessia Fornoni, Youssef H Zeidan
The molecular mechanisms responsible for the development of proteinuria and glomerulosclerosis in radiation nephropathy remain largely unknown. Podocytes are increasingly recognized as key players in the pathogenesis of proteinuria in primary and secondary glomerular disorders. The lipid-modulating enzyme sphingomyelin phosphodiesterase acid-like 3B (SMPDL3b) is a key determinant of podocyte injury and a known off target of the anti-CD20 antibody rituximab (RTX). The current study investigates the role of sphingolipids in radiation-induced podocytopathy...
November 11, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27805006/staurosporines-decrease-ormdl-proteins-and-enhance-sphingomyelin-synthesis-resulting-in-depletion-of-plasmalemmal-phosphatidylserine
#18
Masashi Maekawa, Minhyoung Lee, Kuiru Wei, Neale D Ridgway, Gregory D Fairn
Accumulation of phosphatidylserine in the inner leaflet of the plasma membrane is a hallmark of eukaryotes. Sublethal levels of staurosporine and related compounds deplete phosphatidylserine from the plasma membrane and abrogate K-Ras signaling. Here, we report that low-dose staurosporine and related compounds increase sphingomyelin mass. Mass-spectrometry and metabolic tracer analysis revealed an increase in both the levels and rate of synthesis of sphingomyelin in response to sublethal staurosporine. Mechanistically, it was determined that the abundance of the ORMDL proteins, which negatively regulate serine-palmitoyltransferase, are decreased by low-dose staurosporine...
November 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27802163/acid-sphingomyelinase-is-required-for-cell-surface-presentation-of-met-receptor-tyrosine-kinase-in-cancer-cells
#19
Linyu Zhu, Xiahui Xiong, Yongsoon Kim, Naomi Okada, Fei Lu, Hui Zhang, Hong Sun
Receptor tyrosine kinases (RTKs) are embedded in the lipid bilayer of the plasma membrane, but the specific roles of various lipids in cell signaling remain largely uncharacterized. We have previously found that acid sphingomyelinase (ASM; also known as SMPD1) regulates the conserved DAF-2 (the ortholog IGF-1R in mammals) RTK signaling pathway in Caenorhabditis elegans How ASM and its catalytic products, ceramides, control RTK signaling pathways remain unclear. Here, we report that ASM regulates the homeostasis of Met, an RTK that is frequently overexpressed in various cancers...
November 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27771292/ceramidases-roles-in-sphingolipid-metabolism-and-in-health-and-disease
#20
REVIEW
Nicolas Coant, Wataru Sakamoto, Cungui Mao, Yusuf A Hannun
Over the past three decades, extensive research has been able to determine the biologic functions for the main bioactive sphingolipids, namely ceramide, sphingosine, and sphingosine 1-phosphate (S1P) (Hannun, 1996; Hannun et al., 1986; Okazaki et al., 1989). These studies have managed to define the metabolism, regulation, and function of these bioactive sphingolipids. This emerging body of literature has also implicated bioactive sphingolipids, particularly S1P and ceramide, as key regulators of cellular homeostasis...
January 2017: Advances in Biological Regulation
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