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https://www.readbyqxmd.com/read/28430167/induced-pluripotent-stem-cell-modeling-of-gaucher-s-disease-what-have-we-learned
#1
REVIEW
Dino Matias Santos, Gustavo Tiscornia
Gaucher's disease (GD) is the most frequently inherited lysosomal storage disease, presenting both visceral and neurologic symptoms. Mutations in acid β-glucocerebrosidase disrupt the sphingolipid catabolic pathway promoting glucosylceramide (GlcCer) accumulation in lysosomes. Current treatment options are enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). However, neither of these approaches is effective in treating the neurological aspect of the disease. The use of small pharmacological compounds that act as molecular chaperones is a promising approach that is still experimental...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28427052/glucosylceramide-critically-contributes-to-the-host-defense-of-cystic-fibrosis-lungs
#2
Barbara Kovacic, Carolin Sehl, Barbara Wilker, Markus Kamler, Katrin Anne Becker, Erich Gulbins
BACKGROUND: Cystic fibrosis (CF) is the most common autosomal-recessive disorder in western countries. Previous studies have demonstrated an important role of sphingolipids in the pathophysiology of cystic fibrosis. It has been shown that ceramide has a central role in various pulmonary infections, including those with Pseudomonas aeruginosa (P. aeruginosa). Ceramide is accumulated in the airways of CF mice and patients. However, little is known about a potential role of glucosylceramide in cystic fibrosis...
March 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28424433/-investigating-the-role-of-ceramide-metabolism-associated-cers5-lass5-gene-in-atherosclerosis-pathogenesis-in-endothelial-cells
#3
Neslihan Çoban, Filiz Güçlü Geyik, Özlem Yıldırım, Nihan Erginel Ünaltuna
OBJECTIVE: Ceramide, the backbone of sphingolipids, is the key component affecting atherosclerotic changes through its important second-messenger role. Previous studies have demonstrated protective role of AMP-activated protein kinase (AMPK) genes in regulating atherosclerosis and hypertension. Ceramide synthase 5 (LASS5 or CERS5) gene has function in de novo synthesis of ceramide, and has indirect effect on AMPK gene. Aim of the present study was to identify role of LASS5 gene in atherosclerosis...
March 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/28421200/detection-of-urine-metabolites-in-a-rat-model-of-chronic-fatigue-syndrome-before-and-after-exercise
#4
Changzhuan Shao, Yiming Ren, Zinan Wang, Chenzhe Kang, Hongke Jiang, Aiping Chi
Purpose. The aim of the present study was to elucidate the metabolic mechanisms associated with chronic fatigue syndrome (CFS) via an analysis of urine metabolites prior to and following exercise in a rat model. Methods. A rat model of CFS was established using restraint-stress, forced exercise, and crowded and noisy environments over a period of 4 weeks. Behavioral experiments were conducted in order to evaluate the model. Urine metabolites were analyzed via gas chromatography-mass spectrometry (GC-MS) in combination with multivariate statistical analysis before and after exercise...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28420720/a-phase-i-study-of-abc294640-a-first-in-class-sphingosine-kinase-2-inhibitor-in-patients-with-advanced-solid-tumors
#5
Carolyn D Britten, Melanie B Thomas, Elizabeth Garrett-Mayer, Steven H Chin, Keisuke Shirai, Besim Ogretmen, Tricia A Bentz, Alan Brisendine, Kate Anderton, Susan L Cusack, Lynn W Maines, Yan Zhuang, Charles D Smith
Purpose:  Sphingosine kinases (SK1 and SK2) regulate tumor growth by generating the mitogenic and pro-inflammatory lipid sphingosine 1-phosphate (S1P). This phase I study investigated the safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of ABC294640, a first-in-class orally-available inhibitor of SK2.  <p>Experimental Design:  Escalating doses of ABC294640 were administered orally to patients with advanced solid tumors in sequential cohorts at the following dose levels: 250 mg qd, 250 mg bid, 500 mg bid and 750 mg bid, continuously in cycles of 28 days...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28418859/serum-metabolomics-differentiating-pancreatic-cancer-from-new-onset-diabetes
#6
Xiangyi He, Jie Zhong, Shuwei Wang, Yufen Zhou, Lei Wang, Yongping Zhang, Yaozong Yuan
To establish a screening strategy for pancreatic cancer (PC) based on new-onset diabetic mellitus (NO-DM), serum metabolomics analysis and a search for the metabolic pathways associated with PC related DM were performed. Serum samples from patients with NO-DM (n = 30) and patients with pancreatic cancer and NO-DM were examined by liquid chromatography-mass spectrometry. Data were analyzed using principal components analysis (PCA) and orthogonal projection to latent structures (OPLS) of the most significant metabolites...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415015/lipidomics-by-ultrahigh-performance-liquid-chromatography-high-resolution-mass-spectrometry-and-its-application-to-complex-biological-samples
#7
Alexander Triebl, Martin Trötzmüller, Jürgen Hartler, Tatjana Stojakovic, Harald C Köfeler
An improved approach for selective and sensitive identification and quantitation of lipid molecular species using reversed phase chromatography coupled to high resolution mass spectrometry was developed. The method is applicable to a wide variety of biological matrices using a simple liquid-liquid extraction procedure. Together, this approach combines multiple selectivity criteria: Reversed phase chromatography separates lipids according to their acyl chain length and degree of unsaturation and is capable of resolving positional isomers of lysophospholipids, as well as structural isomers of diacyl phospholipids and glycerolipids...
March 24, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28409682/distinct-serum-sphingolipid-profiles-among-school-aged-children-with-exercise-induced-wheeze-and-asthma-persistence
#8
Matthew S Perzanowski, Jennie G Ono, Luis M Acosta, Benjamin I Kim, Adnan Divjan, Rachel Miller, Andrew Rundle, Stefan Worgall, Tilla S Worgall
No abstract text is available yet for this article.
April 15, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28409209/2-acetyl-5-tetrahydroxybutyl-imidazole-thi-protects-661w-cells-against-oxidative-stress
#9
Carlotta Fabiani, Aida Zulueta, Fabiola Bonezzi, Josefina Casas, Riccardo Ghidoni, Paola Signorelli, Anna Caretti
Retinal degeneration and in particular retinitis pigmentosa (RP) is associated to ceramide (Cer) accumulation and cell death induction. Cer and sphingosine-1-phosphate (S1P) belong to the sphingolipids class and exert a pro-apoptotic and pro-survival activity, respectively. Our aim is to target sphingolipid metabolism by inhibiting S1P lyase that regulates one of the S1P degradation pathways, to reduce retinal photoreceptor damage. The murine 661W cone-like cell line was pretreated with THI, an inhibitor of S1P lyase and exposed to H2O2-induced oxidative stress...
April 13, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28409208/inhibitors-of-ceramide-de-novo-biosynthesis-rescue-damages-induced-by-cigarette-smoke-in-airways-epithelia
#10
Aida Zulueta, Anna Caretti, Giuseppe Matteo Campisi, Andrea Brizzolari, Jose Luis Abad, Rita Paroni, Paola Signorelli, Riccardo Ghidoni
Exposure to cigarette smoke represents the most important risk factor for the development of chronic obstructive pulmonary disease (COPD). COPD is characterized by chronic inflammation of the airways, imbalance of proteolytic activity resulting in the destruction of lung parenchyma, alveolar hypoxia, oxidative stress, and apoptosis. Sphingolipids are structural membrane components whose metabolism is altered during stress. Known as apoptosis and inflammation inducer, the sphingolipid ceramide was found to accumulate in COPD airways and its plasma concentration increased as well...
April 13, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28409005/plasma-sphingolipids-in-hiv-associated-chronic-obstructive-pulmonary-disease
#11
Shane Hodgson, Timothy J Griffin, Cavan Reilly, Stephen Harvey, Bruce A Witthuhn, Brian J Sandri, Ken M Kunisaki, Chris H Wendt
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity in persons living with HIV (PLWH) and HIV appears to uniquely cause COPD, independent of smoking. The mechanisms by which HIV leads to COPD are not clear. The objective of this study was to identify metabolomic biomarkers and potential mechanistic pathways of HIV-associated COPD (HIV-COPD). METHODS: We performed case-control metabolite profiling via mass spectrometry in plasma from 38 individuals with HIV-COPD (cases), comparing to matched controls with/without HIV and with/without COPD...
2017: BMJ Open Respiratory Research
https://www.readbyqxmd.com/read/28405720/ceramide-synthase-2-deficiency-aggravates-aom-dss-induced-colitis-in-mice-role-of-colon-barrier-integrity
#12
Stephanie Oertel, Klaus Scholich, Andreas Weigert, Dominique Thomas, Julia Schmetzer, Sandra Trautmann, Marthe-Susanna Wegner, Heinfried H Radeke, Natalie Filmann, Bernhard Brüne, Gerd Geisslinger, Irmgard Tegeder, Sabine Grösch
Loss of intestinal barrier functions is a hallmark of inflammatory bowel disease like ulcerative colitis. The molecular mechanisms are not well understood, but likely involve dysregulation of membrane composition, fluidity, and permeability, which are all essentially regulated by sphingolipids, including ceramides of different chain length and saturation. Here, we used a loss-of-function model (CerS2(+/+) and CerS2(-/-) mice) to investigate the impact of ceramide synthase 2, a key enzyme in the generation of very long-chain ceramides, in the dextran sodium salt (DSS) evoked model of UC...
April 12, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28404749/diffusion-of-lipids-and-gpi-anchored-proteins-in-actin-free-plasma-membrane-vesicles-measured-by-sted-fcs
#13
Falk Schneider, Dominic Waithe, Mathias P Clausen, Silvia Galiani, Thomas Koller, Gunes Ozhan, Christian Eggeling, Erdinc Sezgin
Diffusion and interaction dynamics of molecules at the plasma membrane play an important role in cellular signalling, and they are suggested to be strongly associated with the actin cytoskeleton. Here, we utilise super-resolution STED microscopy combined with fluorescence correlation spectroscopy (STED-FCS) to access and compare the diffusion characteristics of fluorescent lipid analogues and GPI-anchored proteins (GPI-APs) in the live cell plasma membrane and in actin cytoskeleton-free cell-derived giant plasma membrane vesicles (GPMVs)...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28401432/feasibility-assessment-of-a-maldi-fticr-imaging-approach-for-the-3d-reconstruction-of-a-mouse-lung
#14
E Ellen Jones, Cristine Quiason, Stephanie Dale, Sheerin K Shahidi-Latham
Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) has proven to be a quick, robust, and label-free tool to produce two-dimensional (2D) ion-density maps representing the distribution of a variety of analytes across a tissue section of interest. In addition, three-dimensional (3D) imaging mass spectrometry workflows have been developed that are capable of visualizing these same analytes throughout an entire volume of a tissue rather than a single cross-section. Until recently, the use of Fourier transform ion cyclotron resonance (FTICR) mass spectrometers for 3D volume reconstruction has been impractical due to software limitations, such as inadequate capacity to manipulate the extremely large data files produced during an imaging experiment...
April 11, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28400772/sphingolipids-are-dual-specific-drug-targets-for-the-management-of-pulmonary-infections-perspective
#15
REVIEW
Lalita Sharma, Hridayesh Prakash
Sphingolipids are the major constituent of the mucus secreted by the cells of epithelial linings of lungs where they maintain the barrier functions and prevent microbial invasion. Sphingolipids are interconvertible, and their primary and secondary metabolites have both structural and functional roles. Out of several sphingolipid metabolites, sphingosine-1 phosphate (S1P) and ceramide are central molecules and decisive for sphingolipid signaling. These are produced by enzymatic activity of sphingosine kinase-1 (SK-1) upon the challenge with either biological or physiological stresses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28396835/using-a-biologically-annotated-library-to-analyze-the-anticancer-mechanism-of-serine-palmitoyl-transferase-spt-inhibitors
#16
Osamu Sano, Ken-Ichi Kazetani, Ryutaro Adachi, Osamu Kurasawa, Tomohiro Kawamoto, Hidehisa Iwata
Mechanistic understanding is crucial to anticancer drug discovery. Here, we reveal that inhibition of serine palmitoyl transferase (SPT), the rate-limiting enzyme in sphingolipid synthesis, induced death in a lung cancer cell line via a necrosis-dependent pathway. To elucidate the mechanism of cell death induced by SPT inhibition, a biologically annotated library of diverse compounds was screened with an SPT inhibitor. This analysis identified suppressors of SPT inhibitor-mediated cell death. Further analysis using hit compounds from this screening revealed that SPT inhibitors induce COX-2 expression, leading to necrosis-dependent cell death...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28390177/role-of-the-lysosomal-membrane-protein-cln3-in-the-regulation-of-cathepsin-d-activity
#17
Jaime Cárcel-Trullols, Attila D Kovács, David A Pearce
Among Neuronal Ceroid Lipofuscinoses (NCLs), which are childhood fatal neurodegenerative disorders, the juvenile onset form (JNCL) is the most common. JNCL is caused by recessive mutations in the CLN3 gene. CLN3 encodes a lysosomal/endosomal transmembrane protein but its precise function is not completely known. We have previously reported that in baby hamster kidney (BHK) cells stably expressing myc-tagged human CLN3 (myc-CLN3), hyperosmotic conditions drastically increased myc-CLN3 mRNA and protein expression...
April 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28389479/characterization-of-drosophila-saposin-related-mutants-as-a-model-for-lysosomal-sphingolipid-storage-diseases
#18
Julia Sellin, Heike Schulze, Marie Paradis, Dominic Gosejacob, Cyrus Papan, Andrej Shevchenko, Olympia Ekaterina Psathaki, Achim Paululat, Melanie Thielisch, Konrad Sandhoff, Michael Hoch
Sphingolipidoses are inherited diseases belonging to the class of lysosomal storage diseases (LSDs), which are characterized by the accumulation of indigestible material in the lysosome caused by specific defects in the lysosomal degradation machinery. While some LSDs can be efficiently treated by enzyme replacement therapy (ERT), this is not possible if the nervous system is affected due to the presence of the blood brain barrier. Sphingolipidoses in particular often present as severe, untreatable forms of LSDs with massive sphingolipid and membrane accumulation in lysosomes, neurodegeneration, and very short life expectancy...
April 7, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28384202/plasma-cross-gestational-sphingolipidomic-analyses-reveal-potential-first-trimester-biomarkers-of-preeclampsia
#19
Aneta Dobierzewska, Sony Soman, Sebastian E Illanes, Andrew J Morris
INTRODUCTION: Preeclampsia (PE) is a gestational disorder, manifested in the second half of pregnancy by maternal hypertension, proteinuria and generalized edema. PE is a major cause of maternal and fetal morbidity and mortality, accounting for nearly 40% of all premature births worldwide. Bioactive sphingolipids are emerging as key molecules involved in etiopathogenesis of PE, characterized by maternal angiogenic imbalance and symptoms of metabolic syndrome. The aim of this study was to compare the cross-gestational profile of circulating bioactive sphingolipids in maternal plasma from preeclamptic (PE) versus normotensive control (CTL) subjects with the goal of identifying sphingolipids as candidate first trimester biomarkers of PE for early prediction of the disease...
2017: PloS One
https://www.readbyqxmd.com/read/28383715/dietary-sphingolipids-potential-for-management-of-dyslipidemia-and-nonalcoholic-fatty-liver-disease
#20
Gregory H Norris, Christopher N Blesso
The development of therapeutic approaches aimed at reducing inflammation, improving lipid metabolism, and preventing nonalcoholic fatty liver disease holds significant potential in the management of obesity-associated disease. In this review, the recent basic science and clinical research examining dietary sphingolipid intake and the prevention of dyslipidemia and nonalcoholic fatty liver disease is summarized. Dietary sphingolipids have been shown to dose-dependently reduce the acute intestinal absorption of cholesterol, triglycerides, and fatty acids in rodents...
April 5, 2017: Nutrition Reviews
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