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Sphingomyelin

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https://www.readbyqxmd.com/read/28808666/lipidomic-evaluation-of-feline-neurologic-disease-after-aav-gene-therapy
#1
Heather L Gray-Edwards, Xuntian Jiang, Ashley N Randle, Amanda R Taylor, Taylor L Voss, Aime K Johnson, Victoria J McCurdy, Miguel Sena-Esteves, Daniel S Ory, Douglas R Martin
GM1 gangliosidosis is a fatal lysosomal disorder, for which there is no effective treatment. Adeno-associated virus (AAV) gene therapy in GM1 cats has resulted in a greater than 6-fold increase in lifespan, with many cats remaining alive at >5.7 years of age, with minimal clinical signs. Glycolipids are the principal storage product in GM1 gangliosidosis whose pathogenic mechanism is not completely understood. Targeted lipidomics analysis was performed to better define disease mechanisms and identify markers of disease progression for upcoming clinical trials in humans...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28798317/sphingomyelin-as-a-myelin-biomarker-in-csf-of-acquired-demyelinating-neuropathies
#2
Giovanna Capodivento, Davide Visigalli, Martina Garnero, Roberto Fancellu, Michela Demetra Ferrara, Abdul Basit, Zeeshan Hamid, Vito Paolo Pastore, Silvano Garibaldi, Andrea Armirotti, Gianluigi Mancardi, Carlo Serrati, Elisabetta Capello, Angelo Schenone, Lucilla Nobbio
Fast, accurate and reliable methods to quantify the amount of myelin still lack, both in humans and experimental models. The overall objective of the present study was to demonstrate that sphingomyelin (SM) in the cerebrospinal fluid (CSF) of patients affected by demyelinating neuropathies is a myelin biomarker. We found that SM levels mirror both peripheral myelination during development and small myelin rearrangements in experimental models. As in acquired demyelinating peripheral neuropathies myelin breakdown occurs, SM amount in the CSF of these patients might detect the myelin loss...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794205/the-human-serum-metabolome-of-vitamin-b-12-deficiency-and-repletion-and-associations-with-neurological-function-in-elderly-adults
#3
Alex Brito, Dmitry Grapov, Johannes Fahrmann, Danielle Harvey, Ralph Green, Joshua W Miller, Sergey N Fedosov, Setareh Shahab-Ferdows, Daniela Hampel, Theresa L Pedersen, Oliver Fiehn, John W Newman, Ricardo Uauy, Lindsay H Allen
Background: The specific metabolomic perturbations that occur in vitamin B-12 deficiency, and their associations with neurological function, are not well characterized.Objective: We sought to characterize the human serum metabolome in subclinical vitamin B-12 deficiency and repletion.Methods: A before-and-after treatment study provided 1 injection of 10 mg vitamin B-12 (with 100 mg pyridoxine and 100 mg thiamin) to 27 community-dwelling elderly Chileans (∼74 y old) with vitamin B-12 deficiency, as evaluated with serum vitamin B-12, total plasma homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin...
August 9, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28789691/sex-specific-differences-in-hepatic-and-plasma-lipid-profiles-in-healthy-cats-pre-and-post-spaying-and-neutering-relationship-with-feline-hepatic-lipidosis
#4
Chiara Valtolina, Arie B Vaandrager, Robert P Favier, Maidina Tuohetahuntila, Anne Kummeling, Isabelle Jeusette, Jan Rothuizen, Joris H Robben
BACKGROUND: A link between lipid metabolism and disease has been recognized in cats. Since hepatic lipidosis is a frequent disorder in cats, the aim of the current study was to evaluate liver and plasma lipid dimorphism in healthy cats and the effects of gonadectomy on lipid profiling. From six female and six male cats plasma and liver lipid profiles before and after spaying/neutering were assessed and compared to five cats (three neutered male and two spayed female) diagnosed with hepatic lipidosis...
August 8, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28782808/lipid-composition-of-membrane-microdomains-isolated-detergent-free-from-pufa-supplemented-raw264-7-macrophages
#5
Christine Hellwing, Feven Tigistu-Sahle, Herbert Fuhrmann, Reijo Käkelä, Julia Schumann
Profound alterations in the lipid profile of raft and non-raft plasma membrane microdomains were found when RAW264.7 macrophages were supplemented with polyunsaturated fatty acids (PUFAs) in physiologically relevant concentrations. For the first time lipids in the detergent-free isolated membrane domains of phagocytic immune cells were characterized by mass spectrometry. The extent of remodeling of the membrane lipids differed with different n3 and n6 PUFA supplements. The mildest effects were detected for -linolenic acid (LNA) and linoleic acid (LA), the C18 precursors of the n3 and n6 families, respectively...
August 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28770378/comprehensive-quantitation-using-two-stable-isotopically-labeled-species-and-direct-detection-of-n-acyl-moiety-of-sphingomyelin
#6
Kotaro Hama, Yuko Fujiwara, Hidetsugu Tabata, Hideyo Takahashi, Kazuaki Yokoyama
Sphingomyelin (ceramide-phosphocholine, CerPCho) is a common sphingolipid in mammalian cells and is composed of phosphorylcholine and ceramide as polar and hydrophobic components, respectively. In this study, a qualitative liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS/MS) analysis is proposed in which CerPCho structures were assigned based on product ion spectra corresponding to sphingosylphosphorylcholine and N-acyl moieties. From MS/MS/MS analysis of CerPCho, we observed product ion spectra of the N-acyl fatty acids as [RCO2](-) ions as well as sphingosylphosphorylcholine...
August 2, 2017: Lipids
https://www.readbyqxmd.com/read/28758405/blood-metabolic-signatures-of-body-mass-index-a-targeted-metabolomics-study-in-the-epic-cohort
#7
Marion Carayol, Michael F Leitzmann, Pietro Ferrari, Raul Zamora-Ros, David Achaintre, Magdalena Stepien, Julie A Schmidt, Ruth C Travis, Kim Overvad, Anne Tjønneland, Louise Hansen, Rudolf Kaaks, Tilman Kühn, Heiner Boeing, Ursula Bachlechner, Antonia Trichopoulou, Christina Bamia, Domenico Palli, Claudia Agnoli, Rosario Tumino, Paolo Vineis, Salvatore Panico, J Ramón Quirós, Emilio Sanchez-Cantalejo, José María Huerta, Eva Ardanaz, Larraitz Arriola, Antonio Agudo, Jan Nilsson, Olle Melander, Bas Bueno-de-Mesquita, Petra H Peeters, Nick Wareham, Kay-Tee Khaw, Mazda Jenab, Timothy J Key, Augustin Scalbert, Sabina Rinaldi
OBJECTIVE: Metabolomic is now widely used to characterize metabolic phenotypes associated with lifestyle risk factors such as obesity. The objective of the present study was to explore the associations of body mass index (BMI) with 145 metabolites measured in blood samples in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: Metabolites were measured in blood from 392 men from the Oxford (UK) cohort (EPIC-Oxford) and in 327 control subjects who were part of a nested case-control study on hepatobiliary carcinomas (EPIC-Hepatobiliary)...
July 31, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28758160/sphingomyelin-encrypts-tissue-factor-atp-induced-activation-of-a-smase-leads-to-tissue-factor-decryption-and-microvesicle-shedding
#8
Jue Wang, Usha R Pendurthi, L Vijaya Mohan Rao
A majority of tissue factor (TF) on cell surfaces exists in an encrypted state with minimal to no procoagulant activity. At present, it is unclear whether limited availability of phosphatidylserine (PS) and/or a specific membrane lipid in the outer leaflet of the plasma membrane contributes to TF encryption. Sphingomyelin (SM) is a major phospholipid in the outer leaflet, and SM metabolism is shown to be altered in many disease settings that cause thrombotic disorders. The present study is carried out to investigate the effect of SM metabolism on TF activity and TF(+) microvesicles (MVs) release...
May 23, 2017: Blood Advances
https://www.readbyqxmd.com/read/28752209/plasma-lipidome-analysis-by-liquid-chromatography-high-resolution-mass-spectrometry-and-ion-mobility-of-hypertriglyceridemic-patients-on-extended-release-nicotinic-acid-a-pilot-study
#9
Véronique Ferchaud-Roucher, Mikaël Croyal, Thomas Moyon, Yassine Zair, Michel Krempf, Khadija Ouguerram
BACKGROUND: Plasma high triacylglycerols and low HDL-C concentration are associated with increased cardiovascular events. Extended-release nicotinic acid (ERN) was shown to reduce plasma triacylglycerols and total cholesterol but also to markedly increase high-density lipoprotein-cholesterol (HDL-C). No data on the effect of ERN on different species of triacylglycerol, cholesteryl ester, and phospholipids are available. In this study, we applied a nontargeted lipidomic approach to investigate the plasma and lipoproteins lipids profile of hypertriglyceridemic patients treated with ERN or a placebo in order to identify new lipids markers associated with this treatment...
July 28, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28751253/molecular-mechanisms-of-the-action-of-sphingomyelin-specific-pore-forming-toxin-lysenin
#10
REVIEW
Neval Yilmaz, Akiko Yamaji-Hasegawa, Françoise Hullin-Matsuda, Toshihide Kobayashi
Lysenin, which is an earthworm toxin, strongly binds to sphingomyelin (SM). Lysenin oligomerizes on SM-rich domains and can induce cell death by forming pores in the membrane. In this review, the assembly of lysenin on SM-containing membranes is discussed mostly on the basis of the information gained by atomic force microscopy (AFM). AFM data show that lysenin assembles into a hexagonal close packed (hcp) structure by rapid reorganization of its oligomers on an SM/cholesterol membrane. In case of a phase-separated membrane of SM, lysenin induces phase mixing as a result of pore formation in SM-rich domains, and consequently its hcp assembly covers the entire membrane...
July 24, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28745666/-detection-of-effective-treatment-of-amnestic-mild-cognitive-impairement-with-cereton-by-testing-of-lipids-markers
#11
A V Alesenko, S I Gavrilova, U A Gutner, A O Lebedeva, M A Shupik, I V Kolykhalov, E V Ponomareva, N D Selezneva, Ya B Fedorova
AIM: Determination of effectivity and safety of Cereton (Choline alfoscerate, production by Sotex) 1200 mg/day in the treatment of cognitive functioning disorders in patients with amnestic mild cognitive impairment (aMCI) and determining its influence in the process (after a 3 month course of taking the drug) and 3 months after the end of treatment of aMCI on the change in the content of phosphatidylcholine, sphingomyelin, ceramide-metabolite sphingolipids and the activity of genes controlling the synthesis of enzymes, which control ithe metabolism of sphingomyelin and ceramide (sphingomyelinase and ceramidase)...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28743366/the-enzymatic-sphingomyelin-to-ceramide-conversion-increases-the-shear-membrane-viscosity-at-the-air-water-interface
#12
REVIEW
Elisa R Catapano, Paolo Natale, Francisco Monroy, Iván López-Montero
Whereas most of lipids have viscous properties and they do not have significant elastic features, ceramides behave as very rigid solid assemblies, displaying viscoelastic behaviour at physiological temperatures. The present review addresses the surface rheology of lipid binary mixtures made of sphingomyelin and ceramide. However, ceramide is formed by the enzymatic cleavage of sphingomyelin in cell plasma membranes. The consequences of the enzymatically-driven ceramide formation involve mechanical alterations of the embedding membrane...
July 19, 2017: Advances in Colloid and Interface Science
https://www.readbyqxmd.com/read/28742512/the-sphingomyelin-synthase-family-proteins-diseases-and-inhibitors
#13
Yang Chen, Yu Cao
Sphingomyelin (SM) is among the most important biomolecules in eukaryotes and acts as both constructive components and signal carrier in physiological process. SM is catalyzed by a membrane protein family, sphingomyelin synthases (SMSs), consisting of three members, SMS1, SMS2 and SMSr. SMSs modulate sphingomyelin and other sphingolipids levels, thereby regulating membrane mobility, ceramide-dependent apoptosis and DAG-dependent signaling pathway. SMSs was found associated with various diseases. Downregulation of SMS2 activity results in protective effects against obesity, atherosclerosis, and diabetes, makes SMS2 inhibitors potential medicines...
July 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28741687/a-distinct-plasma-lipid-signature-associated-with-poor-prognosis-in-castration-resistant-prostate-cancer
#14
H-M Lin, K L Mahon, J M Weir, P A Mundra, C Spielman, K Briscoe, H Gurney, G Mallesara, G Marx, M R Stockler, PRIMe Consortium, R G Parton, A J Hoy, R J Daly, P J Meikle, L G Horvath
Lipids are known to influence tumour growth, inflammation, and chemoresistance. However, the association of circulating lipids with the clinical outcome of metastatic castration-resistant prostate cancer (CRPC) is unknown. We investigated associations between the plasma lipidome and clinical outcome in CRPC. Lipidomic profiling by liquid chromatography-tandem mass spectrometry was performed on plasma samples from a Phase 1 discovery cohort of 96 CRPC patients. Results were validated in an independent Phase 2 cohort of 63 CRPC patients...
July 25, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28740728/dipole-modifiers-regulate-lipid-lateral-heterogeneity-in-model-membranes
#15
S S Efimova, O S Ostroumova
In this study we report on experimental observations of giant unilamellar liposomes composed of ternary mixtures of cholesterol (Chol), phospholipids with relatively low Tmelt (DOPC, POPC, or DPoPC) and high Tmelt (sphingomyelin (SM), or tetramyristoyl cardiolipin (TMCL)) and their phase behaviors in the presence and absence of dipole modifiers. It was shown that the ratios of liposomes exhibiting noticeable phase separation decrease in the series POPC, DOPC, DPoPC regardless of any high-Tmelt lipid. Substitution of SM for TMCL led to increased lipid phase segregation...
April 2017: Acta Naturae
https://www.readbyqxmd.com/read/28733574/metabolomic-characteristics-of-cholesterol-induced-non-obese-nonalcoholic-fatty-liver-disease-in-mice
#16
Lan N Tu, Megan R Showalter, Tomas Cajka, Sili Fan, Viju V Pillai, Oliver Fiehn, Vimal Selvaraj
Nonalcoholic fatty liver disease (NAFLD) in non-obese patients remains a clinical condition with unclear etiology and pathogenesis. Using a metabolomics approach in a mouse model that recapitulates almost all the characteristic features of non-obese NAFLD, we aimed to advance mechanistic understanding of this disorder. Mice fed high fat, high cholesterol, cholate (HFHCC) diet for three weeks consistently developed hepatic pathology similar to NAFLD and nonalcoholic steatohepatitis (NASH) without changes to body weight or fat pad weights...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28726959/association-of-cultured-myotubes-and-fasting-plasma-metabolite-profiles-with-mitochondrial-dysfunction-in-type-2-diabetes-subjects
#17
Mohamad Hafizi Abu Bakar, Mohamad Roji Sarmidi
Accumulating evidence implicates mitochondrial dysfunction-induced insulin resistance in skeletal muscle as the root cause for the greatest hallmarks of type 2 diabetes (T2D). However, the identification of specific metabolite-based markers linked to mitochondrial dysfunction in T2D has not been adequately addressed. Therefore, we sought to identify the markers-based metabolomics for mitochondrial dysfunction associated with T2D. First, a cellular disease model was established using human myotubes treated with antimycin A, an oxidative phosphorylation inhibitor...
July 20, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28718792/recombinant-lipase-from-gibberella-zeae-exhibits-broad-substrate-specificity-a-comparative-study-on-emulsified-and-monomolecular-substrate
#18
Fanghua Wang, Hui Zhang, Zexin Zhao, Ruixia Wei, Bo Yang, Yonghua Wang
Using the classical emulsified system and the monomolecular film technique, the substrate specificity of recombinant Gibberella zeae lipase (rGZEL) that originates from Gibberella zeae was characterized in detail. Under the emulsified reaction system, both phospholipase and glycolipid hydrolytic activities were observed, except for the predominant lipase activity. The optimum conditions for different activity exhibition were also determined. Compared with its lipase activity, a little higher ratio of glycolipid hydrolytic activity (0...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28710349/lipid-driven-nanodomains-in-giant-lipid-vesicles-are-fluid-and-disordered
#19
Alena Koukalová, Mariana Amaro, Gokcan Aydogan, Gerhard Gröbner, Philip T F Williamson, Ilya Mikhalyov, Martin Hof, Radek Šachl
It is a fundamental question in cell biology and biophysics whether sphingomyelin (SM)- and cholesterol (Chol)- driven nanodomains exist in living cells and in model membranes. Biophysical studies on model membranes revealed SM and Chol driven micrometer-sized liquid-ordered domains. Although the existence of such microdomains has not been proven for the plasma membrane, such lipid mixtures have been often used as a model system for 'rafts'. On the other hand, recent super resolution and single molecule results indicate that the plasma membrane might organize into nanocompartments...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709768/plasma-sphingosine-1-phosphate-concentrations-are-associated-with-systolic-heart-failure-in-patients-with-ischemic-heart-disease
#20
Amin Polzin, Kerstin Piayda, Petra Keul, Lisa Dannenberg, Annemarie Mohring, Markus Gräler, Tobias Zeus, Malte Kelm, Bodo Levkau
OBJECTIVE: Sphingosine-1-Phosphate (S1P) is a bioactive sphingolipid with important functions in immunity, inflammation and cardiovascular biology. S1P is associated with prevalence and severity of coronary artery disease and myocardial infarction. However, its relevance in ischemic cardiomyopathy is unknown. We aimed to investigate associations of plasma S1P and other sphingolipids with the extent of heart failure in patients with ischemic heart disease. METHODS AND RESULTS: 74 patients with ischemic heart disease were investigated in this observational study...
July 12, 2017: Journal of Molecular and Cellular Cardiology
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