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Sphingolipids

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https://www.readbyqxmd.com/read/28637533/everybody-needs-sphingolipids-right-mining-for-new-drug-targets-in-protozoan-sphingolipid-biosynthesis
#1
John G M Mina, P W Denny
Sphingolipids (SLs) are an integral part of all eukaryotic cellular membranes. In addition, they have indispensable functions as signalling molecules controlling a myriad of cellular events. Disruption of either the de novo synthesis or the degradation pathways has been shown to have detrimental effects. The earlier identification of selective inhibitors of fungal SL biosynthesis promised potent broad-spectrum anti-fungal agents, which later encouraged testing some of those agents against protozoan parasites...
June 22, 2017: Parasitology
https://www.readbyqxmd.com/read/28629526/erythropoietin-receptor-signaling-and-lipid-rafts
#2
Kathy McGraw, Alan List
Erythropoiesis is tightly regulated by the growth factor erythropoietin (Epo). Signal activation begins when Epo engages its cognate receptor, Epo-R, triggering receptor homodimerization, and recruitment of signaling intermediates including Jak2 that phosphorylates both the receptor cytoplasmic tail and downstream effectors including the transcription factor, STAT5. Transcription factors subsequently activate transcription of prosurvival and prodifferentiation genes responsible for red blood cell production...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28626422/sphingosine-1-phosphate-receptors-do-they-have-a-therapeutic-potential-in-cardiac-fibrosis
#3
REVIEW
Ambra Vestri, Federica Pierucci, Alessia Frati, Lucia Monaco, Elisabetta Meacci
Sphingosine 1-phosphate (S1P) is a bioactive lipid that is characterized by a peculiar mechanism of action. In fact, S1P, which is produced inside the cell, can act as an intracellular mediator, whereas after its export outside the cell, it can act as ligand of specific G-protein coupled receptors, which were initially named endothelial differentiation gene (Edg) and eventually renamed sphingosine 1-phosphate receptors (S1PRs). Among the five S1PR subtypes, S1PR1, S1PR2 and S1PR3 isoforms show broad tissue gene expression, while S1PR4 is primarily expressed in immune system cells, and S1PR5 is expressed in the central nervous system...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28624380/plasma-phospholipids-and-sphingolipids-identify-stent-restenosis-after-percutaneous-coronary-intervention
#4
Song Cui, Kefeng Li, Lawrence Ang, Jinghua Liu, Liqian Cui, Xiantao Song, Shuzheng Lv, Ehtisham Mahmud
OBJECTIVES: The aim of this study was to evaluate the diagnostic utility of plasma metabolomic biomarkers for in-stent restenosis (ISR). BACKGROUND: ISR remains an issue for patients after percutaneous coronary intervention. Identification of biomarkers to predict ISR could be invaluable for patient care. METHODS: Next-generation metabolomic profiling was performed in the discovery phase from the plasma of 400 patients undergoing percutaneous coronary intervention...
June 7, 2017: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28622139/immune-regulation-and-functions-of-eicosanoid-lipid-mediators
#5
Julia Esser-von Bieren
Bioactive lipids regulate most physiological processes, from digestion to blood flow and from hemostasis to labor. Lipid mediators are also involved in multiple pathologies including cancer, autoimmunity or asthma. The pathological roles of lipid mediators are based on their intricate involvement in the immune system, which comprises source and target cells of these mediators. Based on their biosynthetic origin, bioactive lipids can be grouped into different classes (e.g. sphingolipids, formed from sphingosine or eicosanoids, formed from arachidonic acid)...
June 15, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28621883/determination-of-the-serine-palmitoyl-transferase-inhibitor-myriocin-by-electrospray-and-q-trap-mass-spectrometry
#6
Giuseppe Matteo Campisi, Paola Signorelli, Jessica Rizzo, Claudio Ghilardi, Jacopo Antognetti, Anna Caretti, Jelena S Lazarevic, Enrica Strettoi, Elena Novelli, Riccardo Ghidoni, Federico Maria Rubino, Rita Paroni
Myriocin, is a potent inhibitor of serine-palmitoyl-transferase, the first and rate-determining enzyme in the sphingolipids biosynthetic pathway. This study developed, validated and applied a LC-MS/MS method to measure Myriocin in minute specimens of animal tissue. The chemical analog 14-OH-Myriocin is used as the internal standard. The two molecules are extracted from the tissue homogenate by solid-phase extraction, separated by gradient reverse-phase liquid chromatography and measured by negative ion electrospray mass spectrometry in the triple quadrupole...
June 16, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28617863/the-use-of-metabolic-profiling-to-identify-insulin-resistance-in-veal-calves
#7
Andre J Pantophlet, Han Roelofsen, Marcel P de Vries, Walter J J Gerrits, Joost J G C van den Borne, Roel J Vonk
Heavy veal calves (4-6 months old) are at risk of developing insulin resistance and disturbed glucose homeostasis. Prolonged insulin resistance could lead to metabolic disorders and impaired growth performance. Recently, we discovered that heavy Holstein-Friesian calves raised on a high-lactose or high-fat diet did not differ in insulin sensitivity, that insulin sensitivity was low and 50% of the calves could be considered insulin resistant. Understanding the patho-physiological mechanisms underlying insulin resistance and discovering biomarkers for early diagnosis would be useful for developing prevention strategies...
2017: PloS One
https://www.readbyqxmd.com/read/28607453/specific-skeletal-muscle-sphingolipid-compounds-in-energy-expenditure-regulation-and-weight-gain-in-native-americans-of-southwestern-heritage
#8
S Heinitz, P Piaggi, K L Vinales, A Basolo, J Spranger, D Piomelli, J Krakoff, S R Jumpertz von
BACKGROUND/OBJECTIVES: In animal models, a role in the regulation of energy expenditure (EE) has been ascribed to sphingolipids, active components of cell membranes participating in cellular signaling. In humans, it is unknown whether sphingolipids play a role in the modulation of EE and, consequently, influence weight gain. The present study investigated the putative association of EE and weight gain with sphingolipid levels in human skeletal muscle, a component of fat-free mass (the strongest determinant of EE) in adipose tissue and in plasma...
June 13, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28607130/s1pr1-sphingosine-1-phosphate-receptor-1-signaling-regulates-blood-flow-and-pressure
#9
Anna Cantalupo, Antonella Gargiulo, Elona Dautaj, Catherine Liu, Yi Zhang, Timothy Hla, Annarita Di Lorenzo
Nitric oxide is one of the major endothelial-derived vasoactive factors that regulate blood pressure (BP), and the bioactive lipid mediator S1P (sphingosine-1-phosphate) is a potent activator of endothelial nitric oxide synthase through G protein-coupled receptors. Endothelial-derived S1P and the autocrine/paracrine activation of S1PR (S1P receptors) play an important role in preserving vascular functions and BP homeostasis. Furthermore, FTY720 (fingolimod), binding to 4 out of 5 S1PRs recently approved by the Food and Drug Administration to treat autoimmune conditions, induces a modest and transient decrease in heart rate in both animals and humans, suggesting that drugs targeting sphingolipid signaling affect cardiovascular functions in vivo...
June 12, 2017: Hypertension
https://www.readbyqxmd.com/read/28607008/the-dipole-potential-correlates-with-lipid-raft-markers-in-the-plasma-membrane-of-living-cells
#10
Tamás Kovács, Gyula Batta, Florina Zákány, János Szöllősi, Peter Nagy
The dipole potential generating an electric field much stronger than any other type of membrane potential influences a wide array of phenomena ranging from passive permeation to voltage-dependent conformational changes of membrane proteins. It is generated by the ordered orientation of lipid carbonyl and membrane-attached water dipole moments. Theoretical considerations and indirect experimental evidence obtained in model membranes suggest that the dipole potential is larger in liquid-ordered domains believed to correspond to lipid rafts in cell membranes...
June 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28603987/pharmacophore-identification-and-scaffold-exploration-to-discover-novel-potent-and-chemically-stable-inhibitors-of-acid-ceramidase-in-melanoma-cells
#11
Jose Antonio Ortega, Jose M Arencibia, Giuseppina La Sala, Marco Borgogno, Inga Bauer, Luca Bono, Clarissa Braccia, Andrea Armirotti, Stefania Girotto, Anand Ganesan, Marco De Vivo
Acid ceramidase (AC) hydrolyses ceramides, which are central lipid messengers for metabolism and signaling of sphingolipids. A growing body of evidence links deregulation of sphingolipids to several diseases, including cancer. Indeed, AC expression is abnormally high in melanoma cells. AC inhibition may thus be key to treating malignant melanoma. Here, we have used a systematic scaffold exploration to design a general pharmacophore for AC inhibition. This pharmacophore comprises a 6+5 fused ring heterocycle linked to an aliphatic substituent via a urea moiety...
June 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28600071/synthetic-antimicrobial-peptides-of-the-halictines-family-disturb-the-membrane-integrity-of-candida-cells
#12
Marie Kodedová, Hana Sychrová
We compared the potency of four derivatives of the antimicrobial peptide halictine-2 against six Candida species. Observed activity was peptide and species specific. Halictines rapidly permeabilized cell membranes and caused the leakage of cytosolic components. Their killing potential was enhanced by the commercial antimicrobial agent octenidine dihydrochloride. The effect on C. glabrata cells did not depend on the activity of Cdr pumps, but was influenced by their lipid composition. The pre-treatment of cells with myriocin, an inhibitor of sphingolipid synthesis, enhanced the peptides' activity, whereas pre-treatment with terbinafine and fluconazole, inhibitors of sterol synthesis, significantly weakened their efficacy...
June 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28598856/glucocerebrosidase-mutations-in-parkinson-disease
#13
Grace O'Regan, Ruth-Mary deSouza, Roberta Balestrino, A H Schapira
Following the discovery of a higher than expected incidence of Parkinson Disease (PD) in Gaucher disease, a lysosomal storage disorder, mutations in the glucocerebrocidase (GBA) gene, which encodes a lysosomal enzyme involved in sphingolipid degradation were explored in the context of idiopathic PD. GBA mutations are now known to be the single largest risk factor for development of idiopathic PD. Clinically, on imaging and pharmacologically, GBA PD is almost identical to idiopathic PD. In patients with a known GBA mutation, it is possible to monitor for prodromal signs of PD...
June 7, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28598843/a-lipidomics-approach-to-assess-the%C3%A2-association-between-plasma-sphingolipids-and-verbal-memory-performance-in-coronary-artery-disease-patients-undertaking-cardiac-rehabilitation-a-c18-0-signature-for%C3%A2-cognitive-response-to-exercise
#14
Mahwesh Saleem, Nathan Herrmann, Adam Dinoff, Michelle M Mielke, Paul I Oh, Prathiba Shammi, Xingshan Cao, Swarajya Lakshmi Vattem Venkata, Norman J Haughey, Krista L Lanctôt
BACKGROUND: Early subtle deficits in verbal memory, which may indicate early neural risk, are common in patients with coronary artery disease (CAD). While exercise can improve cognition, cognitive response to exercise is heterogeneous. Sphingolipids have been associated with the development and progression of CAD, and impairments in sphingolipid metabolism may play roles in neurodegeneration and in the neural adaptation response to exercise. OBJECTIVE: In this study, change in plasma concentrations of sphingolipids was assessed in relation to change in verbal memory performance and in other cognitive domains among CAD subjects undertaking a 6-month cardiac rehabilitation (CR) program...
June 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28596734/characterization-and-expression-of-sphingosine-1-phosphate-receptors-in-human-and-rat-heart
#15
Naseer Ahmed, Daniele Linardi, Ilaria Decimo, Riffat Mehboob, Mebratu A Gebrie, Giulio Innamorati, Giovanni B Luciani, Giuseppe Faggian, Alessio Rungatscher
Aim: Sphingosine 1-phosphate (S1P), sphingolipid derivatives are known anti-inflammatory, anti-apoptotic, and anti-oxidant agent. S1P have been demonstrated to have a role in the cardiovascular system. The purpose of this study was to understand the precise expression and distribution of S1P receptors (S1PRs) in human and rat cardiovascular tissues to know the significance and possible implementation of our experimental studies in rat models. Methods and Results: In this study, we investigated the localization of S1PRs in human heart samples from cardiac surgery department, University of Verona Hospital and rat samples...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28595661/the-antifungal-aureobasidin-a-and-an-analogue-are-active-against-the-protozoan-parasite-toxoplasma-gondii-but-do-not-inhibit-sphingolipid-biosynthesis-corrigendum
#16
A Q I Alqaisi, A J Mbekeani, M Bassas Llorens, A P Elhammer, P W Denny
No abstract text is available yet for this article.
June 9, 2017: Parasitology
https://www.readbyqxmd.com/read/28591608/ceramide-c16-is-a-versatile-modulator-of-phosphatidylethanolamine-polymorphism
#17
Mahmoudreza Doroudgar, Michel Lafleur
Ceramide-C16 (CerC16) is a sphingolipid associated with several diseases like diabetes, obesity, Parkinson disease, and certain types of cancers. As a consequence, research efforts are devoted to identify the impact of CerC16 on the behavior of membranes, and to understand how it is involved in these diseases. In this work, we investigated the impacts of CerC16 (up to 20 mol %) on the lipid polymorphism of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), using differential scanning calorimetry, and sequential (2)H and (31)P solid-state nuclear magnetic resonance spectroscopy...
June 6, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28588581/role-of-sphingosine-1-phosphate-in-mast-cell-functions-and-asthma-and-its-regulation-by-non-coding-rna
#18
REVIEW
Rohit Saluja, Ashok Kumar, Manju Jain, Sudhir K Goel, Aklank Jain
Sphingolipid metabolites are emerging as important signaling molecules in allergic diseases specifically asthma. One of the sphingolipid metabolite, sphingosine-1-phosphate (S1P), is involved in cell differentiation, proliferation, survival, migration, and angiogenesis. In the allergic diseases, alteration of S1P levels influences the differentiation and responsiveness of mast cells (MCs). S1P is synthesized by two sphingosine kinases (SphKs), sphingosine kinase 1, and sphingosine kinase 2. Engagement of IgE to the FcεRI receptor induces the activation of both the SphKs and generates S1P...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28588087/papers-of-note-in-nature546-7656
#19
Annalisa M VanHook
This week's articles highlight the role of follicle-stimulating hormone in postmenopausal adipose tissue accumulation, the importance of a sphingolipid for T cell survival, and the cryo-EM structure of a G protein-coupled receptor complex.
June 6, 2017: Science Signaling
https://www.readbyqxmd.com/read/28588048/the-sphingosine-1-phosphate-break-down-product-2e-hexadecenal-forms-protein-adducts-and-glutathione-conjugates-in-vitro
#20
Fabian Schumacher, Corinna Neuber, Hannah Finke, Kai Nieschalke, Jessica Baesler, Erich Gulbins, Burkhard Kleuser
Sphingosine 1-phosphate (S1P), a bioactive lipid involved in various physiological processes such as cell proliferation and apoptosis, can be irreversibly cleaved by the S1P lyase, yielding phosphoethanolamine and (2E)-hexadecenal (2EHD). The latter metabolite, an α,β-unsaturated fatty aldehyde, may be susceptible to nucleophilic attack by cellular biomolecules. Hence, we studied whether 2EHD forms reaction products with glutathione (GSH) and proteins in vitro Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and stable isotopically labeled reference material, we identified a total of nine novel reaction products of 2EHD in a cell-free approach: two GSH conjugates and seven L-amino acid adducts...
June 6, 2017: Journal of Lipid Research
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