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https://www.readbyqxmd.com/read/28208246/combined-proteome-and-eicosanoid-profiling-approach-for-revealing-implications-of-human-fibroblasts-in-chronic-inflammation
#1
Ammar Tahir, Andrea Bileck, Besnik Muqaku, Laura Niederstaetter, Dominique Kreutz, Rupert L Mayer, Denise Wolrab, Samuel M Meier, Astrid Slany, Christopher Gerner
During inflammation, proteins and lipids act in a concerted fashion, calling for combined analyses. Fibroblasts are powerful mediators of chronic inflammation. However, little is known about eicosanoid formation by human fibroblasts. The aim of this study was to analyze the formation of the most relevant inflammation mediators including proteins and lipids in human fibroblasts upon inflammatory stimulation and subsequent treatment with dexamethasone, a powerful antiphlogistic drug. Label-free quantification was applied for proteome profiling, while an in-house established data-dependent analysis method based on high-resolution mass spectrometry was applied for eicosadomics...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28207776/the-improved-efficacy-of-sifuvirtide-compared-with-enfuvirtide-might-be-related-to-its-selectivity-for-the-rigid-biomembrane-as-determined-through-surface-plasmon-resonance
#2
Ping Cao, Guifang Dou, Yuanguo Cheng, Jinjing Che
Most mechanistic studies on human immunodeficiency virus (HIV) peptide fusion inhibitors have focused on the interactions between fusion inhibitors and viral envelope proteins. However, the interactions of fusion inhibitors with viral membranes are also essential for the efficacy of these drugs. Here, we utilized surface plasmon resonance (SPR) technology to study the interactions between the HIV fusion inhibitor peptides sifuvirtide and enfuvirtide and biomembrane models. Sifuvirtide presented selectivity toward biomembrane models composed of saturated dipalmitoylphosphatidylcholine (DPPC) (32-fold higher compared with unsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine [POPC]) and sphingomyelin (SM) (31-fold higher compared with POPC), which are rigid compositions enriched in the HIV viral membrane...
2017: PloS One
https://www.readbyqxmd.com/read/28202358/a-prospective-multicenter-double-blind-randomized-trial-of-bladder-instillation-of-liposome-formulation-onabotulinumtoxina-for-interstitial-cystitis-bladder-pain-syndrome
#3
Yao-Chi Chuang, Hann-Chorng Kuo
BACKGROUND: Intravesical instillation of liposomal-formulated botulinum toxin A (lipotoxin) has shown therapeutic effects on treatment of refractory overactive bladder without needle injections. We hereby assessed lipotoxin for the treatment of refractory interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: This two-center, double-blind, randomized, placebo-controlled physician-initiated study enrolled patients with refractory IC/BPS. The patients were assigned to intravesical instillation of lipotoxin (onabotulinumtoxinA 200 U with 80mg sphingomyelin) (n=31), onabotulinumtoxinA 200 U in normal saline (n=28), or normal saline alone (n=31)...
February 12, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28196862/mtorc1-activity-is-required-to-maintain-canonical-endocytic-recycling-pathway-against-lysosomal-delivery
#4
Kristin Dauner, Walaa Eid, Riya Raghupathy, John Presley, Xiaohui Zha
The plasma membrane of mammalian cells undergoes constitutive endocytosis, endocytic sorting and recycling, which delivers nutrients to the lysosomes. The receptors, along with membrane lipids, are normally returned to the plasma membrane to sustain this action. It is not known, however, whether this process is influenced by metabolic conditions. Here we report that endocytic recycling requires active mTORC1, a master metabolic sensor. Upon mTORC1 inactivation, either by starvation or by inhibitors, plasma membrane lipids and recycling receptors, such as sphingomyelin and transferrin receptors, are delivered to the lysosomes...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28180139/metabolomic-signatures-associated-with-disease-severity-in-multiple-sclerosis
#5
Pablo Villoslada, Cristina Alonso, Ion Agirrezabal, Ekaterina Kotelnikova, Irati Zubizarreta, Irene Pulido-Valdeolivas, Albert Saiz, Manuel Comabella, Xavier Montalban, Luisa Villar, Jose Carlos Alvarez-Cermeño, Oscar Fernández, Roberto Alvarez-Lafuente, Rafael Arroyo, Azucena Castro
OBJECTIVE: To identify differences in the metabolomic profile in the serum of patients with multiple sclerosis (MS) compared to controls and to identify biomarkers of disease severity. METHODS: We studied 2 cohorts of patients with MS: a retrospective longitudinal cohort of 238 patients and 74 controls and a prospective cohort of 61 patients and 41 controls with serial serum samples. Patients were stratified into active or stable disease based on 2 years of prospective assessment accounting for presence of clinical relapses or changes in disability measured with the Expanded Disability Status Scale (EDSS)...
March 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28167768/high-resolution-imaging-and-quantification-of-plasma-membrane-cholesterol-by-nanosims
#6
Cuiwen He, Xuchen Hu, Rachel S Jung, Thomas A Weston, Norma P Sandoval, Peter Tontonoz, Matthew R Kilburn, Loren G Fong, Stephen G Young, Haibo Jiang
Cholesterol is a crucial lipid within the plasma membrane of mammalian cells. Recent biochemical studies showed that one pool of cholesterol in the plasma membrane is "accessible" to binding by a modified version of the cytolysin perfringolysin O (PFO*), whereas another pool is sequestered by sphingomyelin and cannot be bound by PFO* unless the sphingomyelin is destroyed with sphingomyelinase (SMase). Thus far, it has been unclear whether PFO* and related cholesterol-binding proteins bind uniformly to the plasma membrane or bind preferentially to specific domains or morphologic features on the plasma membrane...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28167702/assessment-of-altered-lipid-homeostasis-by-hilic-ion-mobility-mass-spectrometry-based-lipidomics
#7
Kelly M Hines, Josi Herron, Libin Xu
Ion mobility-mass spectrometry (IM-MS) has proven to be a highly informative technique for the characterization of lipids from cells and tissues. We report the combination of hydrophilic interaction liquid chromatography (HILIC) with traveling wave IM-MS (TWIM-MS) for comprehensive lipidomics analysis. Main lipid categories such as glycerolipids, sphingolipids, and glycerophospholipids are separated on the basis of their lipid backbones in the IM dimension while sub-classes of each category are mostly separated based on their headgroups in the HILIC dimension, demonstrating the orthogonality of HILIC and IM separations...
February 6, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28164012/effect-of-serial-infusions-of-reconstituted-high-density-lipoprotein-cer-001-on-coronary-atherosclerosis-rationale-and-design-of-the-carat-study
#8
Jordan Andrews, Alex Janssan, Tracy Nguyen, Anthony D Pisaniello, Daniel J Scherer, John J P Kastelein, Bela Merkely, Steven E Nissen, Kausik Ray, Gregory G Schwartz, Stephen G Worthley, Connie Keyserling, Jean-Louis Dasseux, Julie Butters, Jacinta Girardi, Rosemary Miller, Stephen J Nicholls
BACKGROUND: High-density lipoprotein (HDL) is believed to have atheroprotective properties, but an effective HDL-based therapy remains elusive. Early studies have suggested that infusion of reconstituted HDL promotes reverse cholesterol transport and vascular reactivity. The CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial (CARAT) is investigating the impact of infusing an engineered pre-beta HDL mimetic containing sphingomyelin (SM) and dipalmitoyl phosphatidlyglycerol (CER-001) on coronary atheroma volume in patients with a recent acute coronary syndrome (ACS)...
February 2017: Cardiovascular Diagnosis and Therapy
https://www.readbyqxmd.com/read/28161835/changes-in-lipid-and-fatty-acid-composition-during-intramacrophagic-transformation-of-leishmania-donovani-complex-promastigotes-into-amastigotes
#9
Hana Bouazizi-Ben Messaoud, Marion Guichard, Philippe Lawton, Isabelle Delton, Samira Azzouz-Maache
Leishmania sp., are trypanosomatid parasites that are phagocytized by human and animal macrophages. Transformation from the vector promastigote stage to the intracellular amastigote host cell stage is mandatory, since development in the host depends on the internalization of the parasite. We identified and analyzed the lipids involved in the promastigote to amastigote transformation process in the Leishmania donovani complex. Four lipid classes, phospholipids, free fatty acids, triglycerides and sterols were studied...
February 4, 2017: Lipids
https://www.readbyqxmd.com/read/28159969/targeted-metabolomics-reveals-early-dominant-optic-atrophy-signature-in-optic-nerves-of-opa1delttag-mice
#10
Juan Manuel Chao de la Barca, Gilles Simard, Emmanuelle Sarzi, Tanguy Chaumette, Guillaume Rousseau, Stéphanie Chupin, Cédric Gadras, Lydie Tessier, Marc Ferré, Arnaud Chevrollier, Valérie Desquiret-Dumas, Naïg Gueguen, Stéphanie Leruez, Christophe Verny, Dan Miléa, Dominique Bonneau, Patrizia Amati-Bonneau, Vincent Procaccio, Christian Hamel, Guy Lenaers, Pascal Reynier, Delphine Prunier-Mirebeau
Purpose: Dominant optic atrophy (MIM No. 165500) is a blinding condition related to mutations in OPA1, a gene encoding a large GTPase involved in mitochondrial inner membrane dynamics. Although several mouse models mimicking the disease have been developed, the pathophysiological mechanisms responsible for retinal ganglion cell degeneration remain poorly understood. Methods: Using a targeted metabolomic approach, we measured the concentrations of 188 metabolites in nine tissues, that is, brain, three types of skeletal muscle, heart, liver, retina, optic nerve, and plasma in symptomatic 11-month-old Opa1delTTAG/+ mice...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28159245/the-miscibility-of-milk-sphingomyelin-and-cholesterol-is-affected-by-temperature-and-surface-pressure-in-mixed-langmuir-monolayers
#11
Ken Cheng, Marie-Hélène Ropers, Christelle Lopez
The miscibility of milk sphingomyelin (milk-SM) and cholesterol was investigated in this study. The effect of different physical states of milk-SM on its interactions with cholesterol was determined by the recording of isotherms of compression of Langmuir films for temperatures above and below the gel to Lα phase transition of milk-SM (Tm∼34°C). For T=15°C<Tm, the liquid expanded (LE) to liquid condensed (LC) phase transition of milk-SM monolayers was observed at surface pressures of 10-15mN/m. For T=43°C>Tm, the milk-SM molecules were in a LE phase regardless of the surface pressure applied...
June 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28156033/amplification-of-a-fret-probe-by-lipid-water-partition-for-the-detection-of-acid-sphingomyelinase-in-live-cells
#12
Thomas Pinkert, David Furkert, Thomas Korte, Andreas Herrmann, Christoph Arenz
Real-time monitoring of acid sphingomyelinase (ASM) activity is crucial for investigating its role in lipid-mediated signaling processes. In this study, we synthesized fluorescent phosphosphingolipids capable of FRET by phosphorodichloridate chemistry. These sphingomyelin analogues are substrates for recombinant human ASM and can be used to monitor ASM activity by fluorescence spectroscopy. Incubation with cell lysates from wild-type and knock-out mice further confirmed probe cleavage to be exclusive to ASM...
February 3, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28151921/a-non-targeted-liquid-chromatographic-mass-spectrometric-metabolomics-approach-for-association-with-coronary-artery-disease-an-identification-of-biomarkers-for-depiction-of-underlying-biological-mechanisms
#13
Xian-Zhao Zhang, Su-Xia Zheng, Ya-Min Hou
BACKGROUND We performed non-targeted metabolomics analysis using liquid chromatography-mass spectrometry coupled technique to explore the biological mechanism of coronary artery disease (CAD) events for improved prediction. MATERIAL AND METHODS We studied the association of CAD events in 4092 individuals and observed the replication of sphingomyelin (28:1), lysophosphatidylcholine (18:2), lysophosphatidylcholine (18:1), and monoglyceride (18:2), which were independent of main CAD risk factors. RESULTS We found that these 4 metabolites were responsible for traditional risk factors and also contributed to the modifications related to reclassification and discrimination...
February 2, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28139067/the-effects-of-graded-levels-of-calorie-restriction-ix-global-metabolomic-screen-reveals-modulation-of-carnitines-sphingolipids-and-bile-acids-in-the-liver-of-c57bl-6-mice
#14
Cara L Green, Sharon E Mitchell, Davina Derous, Yingchun Wang, Luonan Chen, Jing-Dong J Han, Daniel E L Promislow, David Lusseau, Alex Douglas, John R Speakman
Calorie restriction (CR) remains the most robust intervention to extend lifespan and improve health span. Using a global mass spectrometry-based metabolomic approach, we identified 193 metabolites that were significantly differentially expressed (SDE) in the livers of C57BL/6 mice, fed graded levels of CR (10, 20, 30 and 40% CR) compared to mice fed ad libitum for 12 h a day. The differential expression of metabolites also varied with the different feeding groups. Pathway analysis revealed that graded CR had an impact on carnitine synthesis and the carnitine shuttle pathway, sphingosine-1-phosphate (S1P) signalling and methionine metabolism...
January 31, 2017: Aging Cell
https://www.readbyqxmd.com/read/28138018/cellular-uptake-of-clostridium-botulinum-c2-toxin-requires-acid-sphingomyelinase-activity
#15
Masahiro Nagahama, Masaya Takehara, Teruhisa Takagishi, Soshi Seike, Kazuaki Miyamoto, Keiko Kobayashi
Clostridium botulinum C2 toxin consists of an enzyme component (C2I) and a binding component (C2II). Activated C2II (C2IIa) binds to a cell receptor, giving rise to lipid raft-dependent oligomerization, and then it assembles with C2I. The whole toxin complex is then endocytosed into the cytosol, resulting in destruction of the actin cytoskeleton and cell rounding. Here, we showed that C2 toxin requires acid sphingomyelinase (ASMase) activity during internalization. In this study, inhibitors of ASMase and lysosomal exocytosis blocked C2 toxin-induced cell rounding...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28127382/dietary-supplementation-with-bovine-derived-milk-fat-globule-membrane-lipids-promotes-neuromuscular-development-in-growing-rats
#16
James F Markworth, Brenan Durainayagam, Vandre C Figueiredo, Karen Liu, Jian Guan, Alastair K H MacGibbon, Bertram Y Fong, Aaron C Fanning, Angela Rowan, Paul McJarrow, David Cameron-Smith
BACKGROUND: The milk fat globule membrane (MFGM) is primarily composed of polar phospho- and sphingolipids, which have established biological effects on neuroplasticity. The present study aimed to investigate the effect of dietary MFGM supplementation on the neuromuscular system during post-natal development. METHODS: Growing rats received dietary supplementation with bovine-derived MFGM mixtures consisting of complex milk lipids (CML), beta serum concentrate (BSC) or a complex milk lipid concentrate (CMLc) (which lacks MFGM proteins) from post-natal day 10 to day 70...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28126847/lipids-regulate-the-hydrolysis-of-membrane-bound-glucosylceramide-by-lysosomal-%C3%AE-glucocerebrosidase-gba1
#17
Misbaudeen Abdul-Hammed, Bernadette Breiden, Günter Schwarzmann, Konrad Sandhoff
Glucosylceramide is the primary storage lipid in the lysosomes of Gaucher patients and a secondary one in Niemann-Pick disease types A, B and C. The regulatory roles of lipids on the hydrolysis of membrane bound glucosylceramide by glucocerebrosidase GBA1 was probed using a detergent-free liposomal assay. The degradation rarely occurs at uncharged liposomal surfaces in the absence of Sap C. However, anionic lipids stimulate glucosylceramide hydrolysis at low pH by up to 1000 fold depending on the nature and position of the negative charges in their head groups while cationic lipids inhibit the degradation, thus showing the importance of electrostatic interactions between the polycationic GBA1 and the negatively charged vesicle surfaces at low pH...
January 26, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28126480/enzymatic-studies-on-planar-supported-membranes-using-a-widefield-fluorescence-laurdan-generalized-polarization-imaging-approach
#18
Jonathan Brewer, Henrik Seir Thoke, Roberto P Stock, Luis A Bagatolli
We introduce a custom-built instrument designed to perform fast LAURDAN Generalized Polarization (GP) imaging on planar supported membranes. It is mounted on a widefield fluorescence microscope and allows kinetic analysis of the GP function in the millisecond time scale, largely improving the temporal resolution previously achieved using laser scanning based microscopes. A dedicated protocol to calibrate LAURDAN GP data obtained with charge-coupled device (CCD) cameras as detectors is also presented, enabling reliable assignment of GP values in the field of view...
January 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28119456/nectin-like-4-complexes-with-choline-transporter-like-protein-1-and-regulates-schwann-cell-choline-homeostasis-and-lipid-biogenesis-in-vitro
#19
Corey Heffernan, Mohit R Jain, Tong Liu, Hyosung Kim, Kevin Barretto, Hong Li, Patrice Maurel
Nectin-like 4 (Necl4, Cadm4) is a Schwann cell-specific cell adhesion molecule that promotes axo-glial interactions. In vitro and in vivo studies have shown that Necl4 is necessary for proper peripheral nerve myelination. However the molecular mechanisms that are regulated by Necl4 and affect peripheral myelination currently remain unclear. We used an in vitro approach to start identifying some of the mechanisms that could explain Necl4 function. Using mass spectrometry and Western blot techniques, we have identified Choline Transporter-Like 1 (CTL1) as a putative complexing partner with Necl4...
January 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28108287/antitumor-activity-of-a-novel-and-orally-available-inhibitor-of-serine-palmitoyltransferase
#20
Masahiro Yaguchi, Sachio Shibata, Yoshinori Satomi, Megumi Hirayama, Ryutaro Adachi, Yasutomi Asano, Takuto Kojima, Yasuhiro Hirata, Akio Mizutani, Atsushi Kiba, Yoji Sagiya
Metabolic reprogramming is an essential hallmark of neoplasia. Therefore, targeting cancer metabolism, including lipid synthesis, has attracted much interest in recent years. Serine palmitoyltransferase (SPT) plays a key role in the initial and rate-limiting step of de novo sphingolipid biosynthesis, and inhibiting SPT activity prevents the proliferation of certain cancer cells. Here, we identified a novel and orally available SPT inhibitor, compound-2. Compound-2 showed an anti-proliferative effect in several cancer cell models, reducing the levels of the sphingolipids ceramide and sphingomyelin...
January 17, 2017: Biochemical and Biophysical Research Communications
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