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C16 ceramide

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https://www.readbyqxmd.com/read/28179290/fumonisin-b1-inhibits-endoplasmic-reticulum-stress-associated-apoptosis-after-foscanpdt-combined-with-c6-pyridinium-ceramide-or-fenretinide
#1
Nithin B Boppana, Jacqueline M Kraveka, Mehrdad Rahmaniyan, L I Li, Alicja Bielawska, Jacek Bielawski, Jason S Pierce, Jeremy S Delor, Kezhong Zhang, Mladen Korbelik, Duska Separovic
BACKGROUND/AIM: Combining an anticancer agent fenretinide (HPR) or C6-pyridinium ceramide (LCL29) with Foscan-mediated photodynamic therapy (FoscanPDT) is expected to augment anticancer benefits of each substance. We showed that treatment with FoscanPDT+HPR enhanced accumulation of C16-dihydroceramide, and that fumonisin B1 (FB), an inhibitor of ceramide synthase, counteracted caspase-3 activation and colony-forming ability of head and neck squamous cell carcinoma (HNSCC) cells. Because cancer cells appear to be more susceptible to increased levels of the endoplasmic reticulum (ER) stress than normal cells, herein we tested the hypothesis that FoscanPDT combined with HPR or LCL29 induces FB-sensitive ER stress-associated apoptosis that affects cell survival...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28179144/plasma-membrane-reorganization-links-acid-sphingomyelinase-ceramide-to-p38-mapk-pathways-in-endothelial-cells-apoptosis
#2
Colin Niaudet, Stéphanie Bonnaud, Maëva Guillonneau, Sébastien Gouard, Marie-Hélène Gaugler, Soizic Dutoit, Natacha Ripoche, Nolwenn Dubois, Valérie Trichet, Isabelle Corre, François Paris
The p38 MAPK signaling pathway is essential in the cellular response to stress stimuli, in particular in the endothelial cells that are major target of external stress. The importance of the bioactive sphingolipid ceramide generated by acid sphingomyelinase is also firmly established in stress-induced endothelial apoptotic cell death. Despite a suggested link between the p38 MAPK and ceramide pathways, the exact molecular events of this connection remain elusive. In the present study, by using two different activators of p38 MAPK, namely anisomycin and ionizing radiation, we depicted how ceramide generated by acid sphingomyelinase was involved in p38 MAPK-dependent apoptosis of endothelial cells...
February 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28151467/augmented-trophoblast-cell-death-in-preeclampsia-can-proceed-via-ceramide-mediated-necroptosis
#3
Liane Jennifer Bailey, Sruthi Alahari, Andrea Tagliaferro, Martin Post, Isabella Caniggia
Preeclampsia, a serious hypertensive disorder of pregnancy, is characterized by elevated ceramide (CER) content that is responsible for heightened trophoblast cell death rates via apoptosis and autophagy. Whether trophoblast cells undergo necroptosis, a newly characterized form of regulated necrosis, and the potential role of CER in this process remain to be established. Herein, we report that exposure of both JEG3 cells and primary isolated cytotrophoblasts to C16:0 CER in conjunction with a caspase-8 inhibitor (Q-VD-OPh) promoted necroptotic cell death, as evidenced by increased expression and association of receptor-interacting protein kinases RIP1 and RIP3, as well as phosphorylation of mixed lineage kinase domain-like (MLKL) protein...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28134039/dysregulations-in-circulating-sphingolipids-associate-with-disease-activity-indices-in-female-patients-with-systemic-lupus-erythematosus-a-cross-sectional-study
#4
A Checa, H Idborg, A Zandian, D Garcia Sar, I Surowiec, J Trygg, E Svenungsson, P-J Jakobsson, P Nilsson, I Gunnarsson, C E Wheelock
Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28112248/mechanistic-interplay-between-ceramide-and-insulin-resistance
#5
Federico Reali, Melissa J Morine, Ozan Kahramanoğulları, Suryaprakash Raichur, Hans-Christoph Schneider, Daniel Crowther, Corrado Priami
Recent research adds to a growing body of literature on the essential role of ceramides in glucose homeostasis and insulin signaling, while the mechanistic interplay between various components of ceramide metabolism remains to be quantified. We present an extended model of C16:0 ceramide production through both the de novo synthesis and the salvage pathways. We verify our model with a combination of published models and independent experimental data. In silico experiments of the behavior of ceramide and related bioactive lipids in accordance with the observed transcriptomic changes in obese/diabetic murine macrophages at 5 and 16 weeks support the observation of insulin resistance only at the later phase...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28087695/novel-interconnections-in-lipid-metabolism-revealed-by-overexpression-of-sphingomyelin-synthase-1
#6
Gergana M Deevska, Patrick P Dotson, Alexander A Karakashian, Giorgis Isaac, Mark Wrona, Samuel B Kelly, Alfred H Merrill, Mariana N Nikolova-Karakashian
This study investigates the consequences of elevating sphingomyelin synthase 1 (SMS1) activity, which generates the main mammalian sphingolipid, sphingomyelin. HepG2 cells stably transfected with SMS1 (HepG2-SMS1), exhibit elevated enzyme activity in vitro and increased sphingomyelin content (mainly C22:0- and C24:0-sphingomyelin), but lower hexosylceramide (Hex-Cer) levels. HepG2-SMS1 cells have less triacylglycerols than controls but similar diacylglycerol acyltransferase activity, triacylglycerol secretion, and mitochondrial function...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28003342/ceramides-and-mitochondrial-fatty-acid-oxidation-in-obesity
#7
REVIEW
Raquel Fucho, Núria Casals, Dolors Serra, Laura Herrero
Obesity is an epidemic, complex disease that is characterized by increased glucose, lipids, and low-grade inflammation in the circulation, among other factors. It creates the perfect scenario for the production of ceramide, the building block of the sphingolipid family of lipids, which is involved in metabolic disorders such as obesity, diabetes, and cardiovascular disease. In addition, obesity causes a decrease in fatty acid oxidation (FAO), which contributes to lipid accumulation within the cells, conferring more susceptibility to cell dysfunction...
December 21, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27916888/a-topographical-atlas-of-shiga-toxin-2e-receptor-distribution-in-the-tissues-of-weaned-piglets
#8
Daniel Steil, Robert Bonse, Iris Meisen, Gottfried Pohlentz, German Vallejo, Helge Karch, Johannes Müthing
Shiga toxin (Stx) 2e of Stx-producing Escherichia coli (STEC) is the primary virulence factor in the development of pig edema disease shortly after weaning. Stx2e binds to the globo-series glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer, Galα1-4Galβ1-4Glcβ1-1Cer) and globotetraosylceramide (Gb4Cer, GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-1Cer), the latter acting as the preferential Stx2e receptor. We determined Stx receptor profiles of 25 different tissues of a male and a female weaned piglet using immunochemical solid phase binding assays combined with mass spectrometry...
November 30, 2016: Toxins
https://www.readbyqxmd.com/read/27915031/acid-ceramidase-deficiency-is-characterized-by-a-unique-plasma-cytokine-and-ceramide-profile-that-is-altered-by-therapy
#9
Shaalee Dworski, Ping Lu, Aneal Khan, Bruno Maranda, John J Mitchell, Rossella Parini, Maja Di Rocco, Boris Hugle, Makoto Yoshimitsu, Bo Magnusson, Balahan Makay, Nur Arslan, Norberto Guelbert, Karoline Ehlert, Andrea Jarisch, Janet Gardner-Medwin, Rawane Dagher, Maria Teresa Terreri, Charles Marques Lorenco, Lilianna Barillas-Arias, Pranoot Tanpaiboon, Alexander Solyom, James S Norris, Xingxuan He, Edward H Schuchman, Thierry Levade, Jeffrey A Medin
Acid Ceramidase Deficiency (Farber disease, FD) is an ultra-rare Lysosomal Storage Disorder that is poorly understood and often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). Hallmarks of FD are accumulation of ceramides, widespread macrophage infiltration, splenomegaly, and lymphocytosis. The cytokines involved in this abnormal hematopoietic state are unknown. There are dozens of ceramide species and derivatives, but the specific ones that accumulate in FD have not been investigated. We used a multiplex assay to analyze cytokines and mass spectrometry to analyze ceramides in plasma from patients and mice with FD, controls, Farber patients treated by hematopoietic stem cell transplantation (HSCT), JIA patients, and patients with Gaucher disease...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27880732/ceramide-activates-lysosomal-cathepsin-b-and-cathepsin-d-to-attenuate-autophagy-and-induces-er-stress-to-suppress-myeloid-derived-suppressor-cells
#10
Feiyan Liu, Xia Li, Chunwan Lu, Aiping Bai, Jacek Bielawski, Alicja Bielawska, Brendan Marshall, Patricia V Schoenlein, Iryna O Lebedyeva, Kebin Liu
Myeloid-derived suppressor cells (MDSCs) are immune suppressive cells that are hallmarks of human cancer. MDSCs inhibit cytotoxic T lymphocytes (CTLs) and NK cell functions to promote tumor immune escape and progression, and therefore are considered key targets in cancer immunotherapy. Recent studies determined a key role of the apoptosis pathways in tumor-induced MDSC homeostasis and it is known that ceramide plays a key role in regulation of mammalian cell apoptosis. In this study, we aimed to determine the efficacy and underlying molecular mechanism of ceramide in suppression of MDSCs...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27857690/interferon-beta-increases-plasma-ceramides-of-specific-chain-length-in-multiple-sclerosis-patients-unlike-fingolimod-or-natalizumab
#11
Florian M Ottenlinger, Christoph A Mayer, Nerea Ferreirós, Yannick Schreiber, Anja Schwiebs, Katrin G Schmidt, Hanns Ackermann, Josef M Pfeilschifter, Heinfried H Radeke
Fingolimod is used for the treatment of multiple sclerosis (MS) and targets receptors for the bioactive sphingolipid sphingosine-1-phosphate (S1P). Whether fingolimod or other MS therapies conversely affect plasma concentrations of sphingolipids has, however, not yet been analyzed. Herein, we quantified 15 representative sphingolipid species by mass spectrometry in plasma from relapsing-remitting MS patients currently under fingolimod (n = 24), natalizumab (n = 16), or IFN-β (n = 18) treatment. Healthy controls (n = 21) and untreated MS patients (n = 11) served as control groups...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27836988/sphingomyelinase-like-phosphodiesterase-3b-mediates-radiation-induced-damage-of-renal-podocytes
#12
Anis Ahmad, Alla Mitrofanova, Jacek Bielawski, Yidong Yang, Brian Marples, Alessia Fornoni, Youssef H Zeidan
The molecular mechanisms responsible for the development of proteinuria and glomerulosclerosis in radiation nephropathy remain largely unknown. Podocytes are increasingly recognized as key players in the pathogenesis of proteinuria in primary and secondary glomerular disorders. The lipid-modulating enzyme sphingomyelin phosphodiesterase acid-like 3B (SMPDL3b) is a key determinant of podocyte injury and a known off target of the anti-CD20 antibody rituximab (RTX). The current study investigates the role of sphingolipids in radiation-induced podocytopathy...
November 11, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27775668/role-of-intracellular-lipid-logistics-in-the-preferential-usage-of-very-long-chain-ceramides-in-glucosylceramide
#13
Toshiyuki Yamaji, Aya Horie, Yuriko Tachida, Chisato Sakuma, Yusuke Suzuki, Yasunori Kushi, Kentaro Hanada
Ceramide is a common precursor of sphingomyelin (SM) and glycosphingolipids (GSLs) in mammalian cells. Ceramide synthase 2 (CERS2), one of the six ceramide synthase isoforms, is responsible for the synthesis of very long chain fatty acid (C20-26 fatty acids) (VLC)-containing ceramides (VLC-Cer). It is known that the proportion of VLC species in GSLs is higher than that in SM. To address the mechanism of the VLC-preference of GSLs, we used genome editing to establish three HeLa cell mutants that expressed different amounts of CERS2 and compared the acyl chain lengths of SM and GSLs by metabolic labeling experiments...
October 21, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27660431/neutral-sphingomyelinase-2-acid-sphingomyelinase-and-ceramide-levels-in-copd-patients-compared-to-controls
#14
Simon R Lea, Hannah J Metcalfe, Jonathan Plumb, Christian Beerli, Chris Poll, Dave Singh, Katharine H Abbott-Banner
BACKGROUND: Increased pulmonary ceramide levels are suggested to play a causative role in lung diseases including COPD. Neutral sphingomyelinase-2 (nSMase-2) and acid SMase (aSMase), which hydrolyze sphingomyelin to produce ceramide, are activated by a range of cellular stresses, including inflammatory cytokines and pathogens, but notably cigarette smoke appears to only activate nSMase-2. Our primary objective was to investigate nSMase-2 and aSMase protein localization and quantification in lung tissue from nonsmokers (NS), smokers (S), and COPD patients...
2016: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/27639801/an-intestinal-microbiota-farnesoid-x-receptor-axis-modulates-metabolic-disease
#15
REVIEW
Frank J Gonzalez, Changtao Jiang, Andrew D Patterson
The gut microbiota is associated with metabolic diseases including obesity, insulin resistance, and nonalcoholic fatty liver disease, as shown by correlative studies and by transplant of microbiota from obese humans and mice into germ-free mice. Modification of the microbiota by treatment of high-fat diet (HFD)-fed mice with tempol or antibiotics resulted in decreased adverse metabolic phenotypes. This was owing to lower levels of the genera Lactobacillus and decreased bile salt hydrolase (BSH) activity. The decreased BSH resulted in increased levels of tauro-β-muricholic acid (MCA), a substrate of BSH and a potent farnesoid X receptor (FXR) antagonist...
November 2016: Gastroenterology
https://www.readbyqxmd.com/read/27638262/palmitic-acid-feeding-increases-ceramide-supply-in-association-with-increased-milk-yield-circulating-nonesterified-fatty-acids-and-adipose-tissue-responsiveness-to-a-glucose-challenge
#16
J E Rico, A T Mathews, J Lovett, N J Haughey, J W McFadden
Reduced insulin action is a key adaptation that facilitates glucose partitioning to the mammary gland for milk synthesis and enhances adipose tissue lipolysis during early lactation. The progressive recovery of insulin sensitivity as cows advance toward late lactation is accompanied by reductions in circulating nonesterified fatty acids (NEFA) and milk yield. Because palmitic acid can promote insulin resistance in monogastrics through sphingolipid ceramide-dependent mechanisms, palmitic acid (C16:0) feeding may enhance milk production by restoring homeorhetic responses...
November 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/27631392/exploring-the-hydration-method-for-loading-sirna-on-liposomes-the-interplay-between-stability-and-biological-activity-in-human-undiluted-ascites-fluid
#17
George R Dakwar, Kevin Braeckmans, Wim Ceelen, Stefaan C De Smedt, Katrien Remaut
Delivery of small interfering RNA (siRNA) is recently gaining tremendous attention for the treatment of ovarian cancer. The present study investigated the potential of different liposomal formulations composed of (2,3-dioleoyloxy-propyl)-trimethylammonium (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) encapsulating siRNA (hydration method) for their ability to knockdown luciferase (Luc) activity in human ovarian cancer SKOV-3 cells. Fluorescence single particle tracking (fSPT) and fluorescence correlation spectroscopy (FCS) in human-undiluted ascites fluid obtained from a peritoneal carcinomatosis patient revealed that cationic hydra-lipoplexes (HYDRA-LPXs) and HYDRA-LPXs decorated with stable DSPE-PEG (DSPE HYDRA-LPXs) showed high stability during at least 24 h...
September 8, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27623848/cytokine-induced-release-of-ceramide-enriched-exosomes-as-a-mediator-of-cell-death-signaling-in-an-oligodendroglioma-cell-line
#18
Maria Podbielska, Zdzisław M Szulc, Ewa Kurowska, Edward L Hogan, Jacek Bielawski, Alicja Bielawska, Narayan R Bhat
Th1 pro-inflammatory cytokines, i.e., TNF-α and IFN-γ, in combination are known to induce cell death in several cell types, including oligodendrocytes, but the mechanism of their synergistic cytotoxicity is unclear. Although ceramide (Cer) has been implicated in cytokine- and stress-induced cell death, its intracellular levels alone cannot explain cytokine synergy. We considered the possibility that Cer released as part of extracellular vesicles may contribute to cytokine-induced synergistic cell death. Using a human oligodendroglioma (HOG) cell line as a model, here we show that exosomes derived from TNF-α-treated "donor" cells, while being mildly toxic to fresh cultures (similar to individual cytokines), induce enhanced cell death when added to IFN-γ-primed target cultures in a fashion resembling the effect of cytokine combination...
November 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27591968/regulation-of-glucose-homeostasis-and-insulin-action-by-ceramide-acyl-chain-length-a-beneficial-role-for-very-long-chain-sphingolipid-species
#19
Magdalene K Montgomery, Simon H J Brown, Xin Y Lim, Corrine E Fiveash, Brenna Osborne, Nicholas L Bentley, Jeremy P Braude, Todd W Mitchell, Adelle C F Coster, Anthony S Don, Gregory J Cooney, Carsten Schmitz-Peiffer, Nigel Turner
In a recent study, we showed that in response to high fat feeding C57BL/6, 129X1, DBA/2 and FVB/N mice all developed glucose intolerance, while BALB/c mice displayed minimal deterioration in glucose tolerance and insulin action. Lipidomic analysis of livers across these five strains has revealed marked strain-specific differences in ceramide (Cer) and sphingomyelin (SM) species with high-fat feeding; with increases in C16-C22 (long-chain) and reductions in C>22 (very long-chain) Cer and SM species observed in the four strains that developed HFD-induced glucose intolerance...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27506241/orm-expression-alters-sphingolipid-homeostasis-and-differentially-affects-ceramide-synthase-activity
#20
Athen N Kimberlin, Gongshe Han, Kyle D Luttgeharm, Ming Chen, Rebecca E Cahoon, Julie M Stone, Jonathan E Markham, Teresa M Dunn, Edgar B Cahoon
Sphingolipid synthesis is tightly regulated in eukaryotes. This regulation in plants ensures sufficient sphingolipids to support growth while limiting the accumulation of sphingolipid metabolites that induce programmed cell death. Serine palmitoyltransferase (SPT) catalyzes the first step in sphingolipid biosynthesis and is considered the primary sphingolipid homeostatic regulatory point. In this report, Arabidopsis (Arabidopsis thaliana) putative SPT regulatory proteins, orosomucoid-like proteins AtORM1 and AtORM2, were found to interact physically with Arabidopsis SPT and to suppress SPT activity when coexpressed with Arabidopsis SPT subunits long-chain base1 (LCB1) and LCB2 and the small subunit of SPT in a yeast (Saccharomyces cerevisiae) SPT-deficient mutant...
October 2016: Plant Physiology
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