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Plasma membrane ceramide

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https://www.readbyqxmd.com/read/28223543/role-of-caspases-in-cd95-induced-biphasic-activation-of-acid-sphingomyelinase
#1
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...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28214863/stimulation-of-erythrocyte-cell-membrane-scrambling-by-c-reactive-protein
#2
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...
February 14, 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
#3
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
#4
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
#5
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...
January 16, 2017: Progress in Lipid Research
https://www.readbyqxmd.com/read/28078595/method-to-measure-sphingomyelin-synthase-activity-changes-in-response-to-cd95l
#6
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
#7
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...
December 26, 2016: Transfusion
https://www.readbyqxmd.com/read/27872481/imaging-cellular-dynamics-with-spectral-relaxation-imaging-microscopy-distinct-spectral-dynamics-in-golgi-membranes-of-living-cells
#8
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
#9
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
#10
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
#11
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
#12
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...
October 11, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27748893/crosstalk-between-autophagy-and-intracellular-radiation-response-review
#13
Lelin Hu, Hao Wang, Li Huang, Yong Zhao, Junjie Wang
Autophagy induced by radiation is critical to cell fate decision. Evidence now sheds light on the importance of autophagy induced by cancer radiotherapy. Traditional view considers radiation can directly or indirectly damage DNA which can activate DNA damage the repair signaling pathway, a large number of proteins participating in DNA damage repair signaling pathway such as p53, ATM, PARP1, FOXO3a, mTOR and SIRT1 involved in autophagy regulation. However, emerging recent evidence suggests radiation can also cause injury to extranuclear targets such as plasma membrane, mitochondria and endoplasmic reticulum (ER) and induce accumulation of ceramide, ROS, and Ca2+ concentration which activate many signaling pathways to modulate autophagy...
December 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27729449/monitoring-changes-in-the-oligomeric-state-of-a-candidate-endoplasmic-reticulum-er-ceramide-sensor-by-single-molecule-photobleaching
#14
Birol Cabukusta, Jan A Köhlen, Christian P Richter, Changjiang You, Joost C M Holthuis
Single-molecule photobleaching has emerged as a powerful non-invasive approach to extract the stoichiometry of multimeric membrane proteins in their native cellular environment. However, this method has mainly been used to determine the subunit composition of ion channels and receptors at the plasma membrane. Here, we applied single-molecule photobleaching to analyze the oligomeric state of an endoplasmic reticulum (ER) resident candidate ceramide sensor protein, SMSr/SAMD8. Co-immunoprecipitation and chemical cross-linking studies previously revealed that the N-terminal sterile alpha motif (or SAM) domain of SMSr drives self-assembly of the protein into oligomers and that SMSr oligomerization is promoted by curcumin, a drug known to perturb ER ceramide and calcium homeostasis...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27643972/glycosylation-of-inositol-phosphorylceramide-sphingolipids-is-required-for-normal-growth-and-reproduction-in-arabidopsis
#15
Virginia Tartaglio, Emilie A Rennie, Rebecca Cahoon, George Wang, Edward Baidoo, Jennifer C Mortimer, Edgar B Cahoon, Henrik V Scheller
Sphingolipids are a major component of plant plasma membranes and endomembranes, and mediate a diverse range of biological processes. Study of the highly glycosylated glycosyl inositol phosphorylceramide (GIPC) sphingolipids has been slow as a result of challenges associated with the extractability of GIPCs, and their functions in the plant remain poorly characterized. We recently discovered an Arabidopsis GIPC glucuronosyltransferase, INOSITOL PHOSPHORYLCERAMIDE GLUCURONOSYLTRANSFERASE 1 (IPUT1), which is the first enzyme in the GIPC glycosylation pathway...
January 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/27610460/ganglioside-lipid-and-ganglioside-protein-interactions-revealed-by-coarse-grained-and-atomistic-molecular-dynamics-simulations
#16
Ruo-Xu Gu, Helgi I Ingólfsson, Alex H de Vries, Siewert J Marrink, D Peter Tieleman
Gangliosides are glycolipids in which an oligosaccharide headgroup containing one or more sialic acids is connected to a ceramide. Gangliosides reside in the outer leaflet of the plasma membrane and play a crucial role in various physiological processes such as cell signal transduction and neuronal differentiation by modulating structures and functions of membrane proteins. Because the detailed behavior of gangliosides and protein-ganglioside interactions are poorly known, we investigated the interactions between the gangliosides GM1 and GM3 and the proteins aquaporin (AQP1) and WALP23 using equilibrium molecular dynamics simulations and potential of mean force calculations at both coarse-grained (CG) and atomistic levels...
October 4, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27588496/an-oncogenic-role-for-sphingosine-kinase-2
#17
Heidi A Neubauer, Duyen H Pham, Julia R Zebol, Paul A B Moretti, Amanda L Peterson, Tamara M Leclercq, Huasheng Chan, Jason A Powell, Melissa R Pitman, Michael S Samuel, Claudine S Bonder, Darren J Creek, Briony L Gliddon, Stuart M Pitson
While both human sphingosine kinases (SK1 and SK2) catalyze the generation of the pleiotropic signaling lipid sphingosine 1-phosphate, these enzymes appear to be functionally distinct. SK1 has well described roles in promoting cell survival, proliferation and neoplastic transformation. The roles of SK2, and its contribution to cancer, however, are much less clear. Some studies have suggested an anti-proliferative/pro-apoptotic function for SK2, while others indicate it has a pro-survival role and its inhibition can have anti-cancer effects...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27583248/biogenesis-and-function-of-t-cell-derived-exosomes
#18
REVIEW
Leandro N Ventimiglia, Miguel A Alonso
Exosomes are a particular type of extracellular vesicle, characterized by their endosomal origin as intraluminal vesicles present in large endosomes with a multivesicular structure. After these endosomes fuse with the plasma membrane, exosomes are secreted into the extracellular space. The ability of exosomes to carry and selectively deliver bioactive molecules (e.g., lipids, proteins, and nucleic acids) confers on them the capacity to modulate the activity of receptor cells, even if these cells are located in distant tissues or organs...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27527902/comparative-lipidomic-study-of-urothelial-cancer-models-association-with-urothelial-cancer-cell-invasiveness
#19
Yang Yu, Matej Skočaj, Mateja Erdani Kreft, Nataša Resnik, Peter Veranič, Pietro Franceschi, Kristina Sepčić, Graziano Guella
Comparative lipidomic studies were performed across the RT4 versus T24 urothelial cancer cell lines, as models for noninvasive urothelial papilloma cells (with a relatively high level of differentiation) and invasive urothelial carcinoma cells (with low level of differentiation), respectively. The aim was to investigate the differences in lipid profile associated with different levels of urothelial cancer cell invasiveness. The cellular lipidomes were characterized using our previously developed joint methodology of liquid chromatography-mass spectrometry and high-resolution nuclear magnetic resonance, which included analysis of the phospholipids and ceramide-based glycosphingolipids...
October 18, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27499046/blunted-apoptosis-of-erythrocytes-in-mice-deficient-in-the-heterotrimeric-g-protein-subunit-g%C3%AE-i2
#20
Rosi Bissinger, Elisabeth Lang, Mehrdad Ghashghaeinia, Yogesh Singh, Christine Zelenak, Birgit Fehrenbacher, Sabina Honisch, Hong Chen, Hajar Fakhri, Anja T Umbach, Guilai Liu, Rexhep Rexhepaj, Guoxing Liu, Martin Schaller, Andreas F Mack, Adrian Lupescu, Lutz Birnbaumer, Florian Lang, Syed M Qadri
Putative functions of the heterotrimeric G-protein subunit Gαi2-dependent signaling include ion channel regulation, cell differentiation, proliferation and apoptosis. Erythrocytes may, similar to apoptosis of nucleated cells, undergo eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure. Eryptosis may be triggered by increased cytosolic Ca(2+) activity and ceramide. In the present study, we show that Gαi2 is expressed in both murine and human erythrocytes and further examined the survival of erythrocytes drawn from Gαi2-deficient mice (Gαi2(-/-)) and corresponding wild-type mice (Gαi2(+/+))...
August 8, 2016: Scientific Reports
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