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Sphingosine

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https://www.readbyqxmd.com/read/28110073/sphingosine-1-phosphate-improves-endothelialization-with-reduction-of-thrombosis-in-recellularized-human-umbilical-vein-graft-by-inhibiting-syndecan-1-shedding-in-vitro
#1
Kai Hsia, Ming-Jie Yang, Wei-Min Chen, Chao-Ling Yao, Chih-Hsun Lin, Che-Chuan Loong, Yi-Long Huang, Ya-Ting Lin, Arthur D Lander, Hsinyu Lee, Jen-Her Lu
: Sphingosine-1-phosphate (S1P) has been known to promote endothelial cell (EC) proliferation and protect Syndecan-1 (SDC1) from shedding, thereby maintaining this antithrombotic signal. In the present study, we investigated the effect of S1P in the construction of a functional tissue-engineered blood vessel by using human endothelial cells and decellularized human umbilical vein (DHUV) scaffolds. Both human umbilical vein endothelial cells (HUVEC) and human cord blood derived endothelial progenitor cells (EPC) were seeded onto the scaffold with or without the S1P treatment...
January 18, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28109750/phytosphingosine-sphingosine-and-dihydrosphingosine-ceramides-in-model-skin-lipid-membranes-permeability-and-biophysics
#2
Barbora Školová, Andrej Kováčik, Ondřej Tesař, Lukáš Opálka, Kateřina Vávrová
Ceramides based on phytosphingosine, sphingosine and dihydrosphingosine are essential constituents of the skin lipid barrier that protects the body from excessive water loss. The roles of the individual ceramide subclasses in regulating skin permeability and the reasons for C4-hydroxylation of these sphingolipids are not completely understood. We investigated the chain length-dependent effects of dihydroceramides, sphingosine ceramides (with C4-unsaturation) and phytoceramides (with C4-hydroxyl) on the permeability, lipid organization and thermotropic behavior of model stratum corneum lipid membranes composed of ceramide/lignoceric acid/cholesterol/cholesteryl sulfate...
January 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28108260/triple-negative-metastatic-breast-cancer-is-dependent-on-sphks-s1p-signaling-for-growth-and-survival
#3
Aparna Maiti, Kazuaki Takabe, Nitai C Hait
About 40,000 American women die from metastatic breast cancer each year despite advancements in treatment. Approximately, 15% of breast cancers are triple-negative for estrogen receptor, progesterone receptor, and HER2. Triple-negative cancer is characterized by more aggressive, harder to treat with conventional approaches and having a greater possibility of recurrence. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid signaling mediator has emerged as a key regulatory molecule in breast cancer progression...
January 17, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28104532/sphingolipids-and-glycerophospholipids-the-ying-and-yang-of-lipotoxicity-in-metabolic-diseases
#4
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/28104445/the-sh3-domain-of-caskin1-binds-to-lysophosphatidic-acid-suggesting-a-direct-role-for-the-lipid-in-intracellular-signaling
#5
Kitti Koprivanacz, Orsolya Tőke, Balázs Besztercei, Tünde Juhász, László Radnai, Balázs Merő, Judith Mihály, Mária Péter, Gábor Balogh, László Vígh, László Buday, Károly Liliom
Src homology 3 or SH3 domains constitute one of the most common protein domains in signal transduction, generally characterized by their binding to proline-rich sequences on interacting signaling proteins. Caskin1, a scaffold protein regulating cortical actin filaments, enriched in neural synapses in mammals, has an atypical SH3 domain. Key aromatic residues necessary for ligand binding that are present in canonical SH3 domains are missing from Caskin1 SH3. In concordance, proline-rich interacting partner could not be identified yet...
January 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28104351/the-sphingosine-1-phosphate-receptor-1-agonist-sew2871-reduces-tau-ser262-phosphorylation-in-rat-hippocampal-slices
#6
Frédéric St-Cyr Giguère, Suzanne Attiori Essis, Laure Chagniel, Marc Germain, Michel Cyr, Guy Massicotte
Recent studies indicate that Tau phosphorylation can be modulated by the compound FTY720-P, a global sphingosine-1-phosphate receptor (S1PR) agonist. The present work compared the effects of more selective S1PR agonists on Tau properties, using rat hippocampal slices as model system. Whereas Tau phosphorylation was not modified by the S1PR3 agonist CYM5541, Tau-Ser262 phosphorylation was significantly decreased by treatment with the S1PR1 agonist SEW2871. This effect appears to be quite restricted, as no changes in phosphorylation were elicited by the agonist on Tau-Ser199/202, Tau-Ser396 and Tau-Ser404 residues...
January 16, 2017: Brain Research
https://www.readbyqxmd.com/read/28101047/acute-anterior-uveitis-in-a-patient-taking-fingolimod-fty720-for-multiple-sclerosis
#7
Heather Gwen Mack, Melissa Chih-Hui Tien, Owen Bruce White
Fingolimod is an oral sphingosine-1-phosphate (S1P) receptor modulator and the first oral therapy for relapsing-remitting multiple sclerosis. Its use has been complicated by a low rate of cystoid macular edema usually in the first 3 months after commencement of the medication. We report the case of a 34-year-old male with relapsing-remitting multiple sclerosis, who developed acute anterior uveitis on day 5 of fingolimod treatment. He responded to appropriate treatment and cessation of drug, but developed low-grade chronic anterior uveitis without cystoid macular edema...
September 2016: Case Reports in Ophthalmology
https://www.readbyqxmd.com/read/28095439/intracranial-injection-of-dengue-virus-induces-interferon-stimulated-genes-and-cd8-t-cell-infiltration-by-sphingosine-kinase-1-independent-pathways
#8
Wisam H Al-Shujairi, Jennifer N Clarke, Lorena T Davies, Mohammed Alsharifi, Stuart M Pitson, Jillian M Carr
We have previously reported that the absence of sphingosine kinase 1 (SK1) affects both dengue virus (DENV) infection and innate immune responses in vitro. Here we aimed to define SK1-dependancy of DENV-induced disease and the associated innate responses in vivo. The lack of a reliable mouse model with a fully competent interferon response for DENV infection is a challenge, and here we use an experimental model of DENV infection in the brain of immunocompetent mice. Intracranial injection of DENV-2 into C57BL/6 mice induced body weight loss and neurological symptoms which was associated with a high level of DENV RNA in the brain...
2017: PloS One
https://www.readbyqxmd.com/read/28089753/simultaneous-quantitation-of-sphingoid-bases-by-uplc-esi-ms-ms-with-identical-13-c-encoded-internal-standards
#9
M Mirzaian, P Wisse, M J Ferraz, A R A Marques, P Gaspar, S V Oussoren, K Kytidou, J D C Codée, G van der Marel, H S Overkleeft, J M Aerts
Free sphingoid bases (lysosphingolipids) of primary storage sphingolipids are increased in tissues and plasma of several sphingolipidoses. As shown earlier by us, sphingoid bases can be accurately quantified using UPLC-ESI-MS/MS, particularly in combination with identical (13)C-encoded internal standards. The feasibility of simultaneous quantitation of sphingoid bases in plasma specimens spiked with a mixture of such standards is here described. The sensitivity and linearity of detection is excellent for all examined sphingoid bases (sphingosine, sphinganine, hexosyl-sphingosine (glucosylsphingosine), hexosyl2-sphingosine (lactosylsphingosine), hexosyl3-sphingosine (globotriaosylsphingosine), phosphorylcholine-sphingosine) in the relevant concentration range and the measurements show very acceptable intra- and inter-assay variation (<10% average)...
January 12, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28088313/q-space-myelin-map-imaging-for-longitudinal-analysis-of-demyelination-and-remyelination-in-multiple-sclerosis-patients-treated-with-fingolimod-a-preliminary-study
#10
Mariko Tanikawa, Jin Nakahara, Junichi Hata, Shigeaki Suzuki, Kanehiro Fujiyoshi, Hirokazu Fujiwara, Suketaka Momoshima, Masahiro Jinzaki, Masaya Nakamura, Hideyuki Okano, Shinichi Takahashi, Norihiro Suzuki
BACKGROUND: Fingolimod (FTY) is an oral sphingosine-1-phosphate receptor modulator that reduces relapse and slows brain atrophy in multiple sclerosis (MS) patients. In addition, FTY has been shown to enhance remyelination in certain animal models. OBJECTIVE: To analyze feasibility of a novel q-space Myelin Map imaging to monitor demyelination and remyelination under FTY treatment in MS patients. METHODS: Treatment outcomes of 24 consecutive MS patients treated with FTY were analyzed...
January 5, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28081222/at7867-inhibits-human-colorectal-cancer-cells-via-akt-dependent-and-akt-independent-mechanisms
#11
Shihu Zhang, Zhengming Deng, Chen Yao, Ping Huang, Yi Zhang, Shibing Cao, Xiangcheng Li
AKT is often hyper-activated in human colorectal cancers (CRC). This current study evaluated the potential anti-CRC activity by AT7867, a novel AKT and p70S6K1 (S6K1) dual inhibitor. We showed that AT7867 inhibited survival and proliferation of established (HT-29, HCT116 and DLD-1 lines) and primary human CRC cells. Meanwhile, it provoked caspase-dependent apoptosis in the CRC cells. Molecularly, AT7867 blocked AKT-S6K1 activation in CRC cells. Restoring AKT-S6K1 activation, via expression of a constitutively-active AKT1 ("ca-AKT1"), only partially attenuated AT7867-induced HT-29 cell death...
2017: PloS One
https://www.readbyqxmd.com/read/28078995/sphingolipids-in-genetic-and-acquired-forms-of-chronic-kidney-diseases
#12
Norishi Ueda
Sphingolipids (SLs) regulate apoptosis, proliferation, and stress response. SLs, including ceramide, glycosphingolipids (glucosylceramide, lactosylceramide, and gangliosides) and sphingosine-1-phosphate (S1P), play a role in the pathogenesis and progression of genetic (lysosomal storage disease, congenital nephrotic syndrome and polycystic kidney disease) and non-genetic forms of chronic kidney diseases (CKDs). SLs metabolism defects promote complications (cardiovascular events, etc.) via oxidant stress in CKDs...
January 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28077491/sphingosine-1-phosphate-lyase-deficiency-causes-charcot-marie-tooth-neuropathy
#13
Derek Atkinson, Jelena Nikodinovic Glumac, Bob Asselbergh, Biljana Ermanoska, David Blocquel, Regula Steiner, Alejandro Estrada-Cuzcano, Kristien Peeters, Tinne Ooms, Els De Vriendt, Xiang-Lei Yang, Thorsten Hornemann, Vedrana Milic Rasic, Albena Jordanova
OBJECTIVE: To identify the unknown genetic cause in a nuclear family with an axonal form of peripheral neuropathy and atypical disease course. METHODS: Detailed neurologic, electrophysiologic, and neuropathologic examinations of the patients were performed. Whole exome sequencing of both affected individuals was done. The effect of the identified sequence variations was investigated at cDNA and protein level in patient-derived lymphoblasts. The plasma sphingoid base profile was analyzed...
January 11, 2017: Neurology
https://www.readbyqxmd.com/read/28077289/vitamin-d3-protects-against-a%C3%AE-peptide-cytotoxicity-in-differentiated-human-neuroblastoma-sh-sy5y-cells-a-role-for-s1p1-p38mapk-atf4-axis
#14
Federica Pierucci, Mercedes Garcia-Gil, Alessia Frati, Francesca Bini, Maria Martinesi, Eleonora Vannini, Marco Mainardi, Federico Luzzati, Paolo Peretto, Matteo Caleo, Elisabetta Meacci
Besides its classical function of bone metabolism regulation, 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3), acts on a variety of tissues including the nervous system, where the hormone plays an important role as neuroprotective, antiproliferating and differentiating agent. Sphingolipids are bioactive lipids that play critical and complex roles in regulating cell fate. In the present paper we have investigated whether sphingolipids are involved in the protective action of 1,25(OH)2D3. We have found that 1,25(OH)2D3 prevents amyloid-β peptide (Aβ(1-42)) cytotoxicity both in differentiated SH-SY5Y human neuroblastoma cells and in vivo...
January 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28075451/the-role-of-sphingolipid-signalling-in-diabetes%C3%A2-associated-pathologies-review
#15
Mei Li Ng, Carol Wadham, Olga A Sukocheva
Sphingosine kinase (SphK) is an important signalling enzyme that catalyses the phosphorylation of sphingosine (Sph) to form sphingosine‑1‑phosphate (S1P). The multifunctional lipid, S1P binds to a family of five G protein-coupled receptors (GPCRs). As an intracellular second messenger, S1P activates key signalling cascades responsible for the maintenance of sphingolipid metabolism, and has been implicated in the progression of cancer, and the development of other inflammatory and metabolic diseases...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28073248/interplay-of-g-protein-coupled-receptors-with-the-membrane-insights-from-supra-atomic-coarse-grain-molecular-dynamics-simulations
#16
Xavier Periole
G protein-coupled receptors (GPCRs) are central to many fundamental cellular signaling pathways. They transduce signals from the outside to the inside of cells in physiological processes ranging from vision to immune response. It is extremely challenging to look at them individually using conventional experimental techniques. Recently, a pseudo atomistic molecular model has emerged as a valuable tool to access information on GPCRs, more specifically on their interactions with their environment in their native cell membrane and the consequences on their supramolecular organization...
January 11, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28070865/sphingosine-1-phosphate-pretreatment-amends-hypoxia-induced-metabolic-dysfunction-and-impairment-of-myogenic-potential-in-differentiating-c2c12-myoblasts-by-stimulating-viability-calcium-homeostasis-and-energy-generation
#17
Babita Rahar, Sonam Chawla, Sanjay Pandey, Anant Narayan Bhatt, Shweta Saxena
Sphingosine-1-phosphate (S1P) has a role in transpiration in patho-physiological signaling in skeletal muscles. The present study evaluated the pre-conditioning efficacy of S1P in facilitating differentiation of C2C12 myoblasts under a normoxic/hypoxic cell culture environment. Under normoxia, exogenous S1P significantly promoted C2C12 differentiation as evident from morphometric descriptors and differentiation markers of the mature myotubes, but it could facilitate only partial recovery from hypoxia-induced compromised differentiation...
January 9, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28054340/fingolimod-confers-neuroprotection-through-activation-of-rac1-after-experimental-germinal-matrix-hemorrhage-in-rat-pups
#18
William B Rolland, Paul R Krafft, Tim Lekic, Damon Klebe, Julia LeGrand, Abby Jones Weldon, Liang Xu, John H Zhang
Fingolimod, a sphingosine-1-phosphate receptor (S1PR) agonist, is clinically available to treat multiple sclerosis and is showing promise in treating stroke. We investigated if fingolimod provides long-term protection from experimental neonatal germinal matrix hemorrhage (GMH), aiming to support a potential mechanism of acute fingolimod-induced protection. GMH was induced in P7 rats by infusion of collagenase (0.3 U) into the right ganglionic eminence. Animals euthanized at four weeks post-GMH received low or high dose fingolimod (0...
January 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28054036/sphingosine-1-phosphate-in-the-lymphatic-fluid-determined-by-novel-methods
#19
Masayuki Nagahashi, Akimitsu Yamada, Tomoyoshi Aoyagi, Jeremy Allegood, Toshifumi Wakai, Sarah Spiegel, Kazuaki Takabe
BACKGROUND: Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator that regulates many physiological and pathological processes. It has been suggested that S1P gradient with high concentrations in the blood and lymphatic fluid and low concentrations in the peripheral tissue plays important roles in immune cell trafficking and potentially cancer progression. However, only a few reports have assessed S1P levels in the lymphatic fluid due to lack of an established easy-to-use method...
December 2016: Heliyon
https://www.readbyqxmd.com/read/28052056/genome-wide-in-vivo-screen-identifies-novel-host-regulators-of-metastatic-colonization
#20
Louise van der Weyden, Mark J Arends, Andrew D Campbell, Tobias Bald, Hannah Wardle-Jones, Nicola Griggs, Martin Del Castillo Velasco-Herrera, Thomas Tüting, Owen J Sansom, Natasha A Karp, Simon Clare, Diane Gleeson, Edward Ryder, Antonella Galli, Elizabeth Tuck, Emma L Cambridge, Thierry Voet, Iain C Macaulay, Kim Wong, Sanger Mouse Genetics Project, Sarah Spiegel, Anneliese O Speak, David J Adams
Metastasis is the leading cause of death for cancer patients. This multi-stage process requires tumour cells to survive in the circulation, extravasate at distant sites, then proliferate; it involves contributions from both the tumour cell and tumour microenvironment ('host', which includes stromal cells and the immune system). Studies suggest the early steps of the metastatic process are relatively efficient, with the post-extravasation regulation of tumour growth ('colonization') being critical in determining metastatic outcome...
January 4, 2017: Nature
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