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C16 ceramide

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
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...
September 14, 2016: Gastroenterology
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...
September 13, 2016: Journal of Dairy Science
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
Maria Podbielska, Zdzislaw 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...
September 13, 2016: Journal of Lipid Research
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...
August 31, 2016: Biochimica et Biophysica Acta
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
Tore Skotland, Kim Ekroos, Simona Kavaliauskiene, Jonas Bergan, Dimple Kauhanen, Tuulia Lintonen, Kirsten Sandvig
In this study we used water soluble stable mass isotope precursors to measure the turnover of endogenous ceramide and glycosphingolipids (GSLs) in HEp-2 cells. Cells incubated in the presence of [(13)C-U]glucose showed rapid incorporation of hexose residues with an increased mass of 6Da into GSLs. Different turnover rates of GSL classes and their molecular species were observed. Approximately 30% of the glucosylceramide (GlcCer), 50% of the lactosylceramide (LacCer) and 50% of the globotriaosylceramide (Gb3) species showed a much slower turnover than the rest...
June 27, 2016: Journal of Molecular Biology
Z Jiang, F Li, Y Wan, Z Han, W Yuan, L Cao, Y Deng, X Peng, F Chen, X Fan, X Liu, G Dai, Y Wang, Q Zeng, Y Shi, Z Zhou, Y Chen, W Xu, S Luo, S Chen, X Ye, X Mo, X Wu, Y Li
Longevity Assurance 5 (LASS5), a member of the LASS/Ceramide Synthases family, synthesizes C16-ceramide and is implicated in tumor biology. However, its precise role is not yet well understood. A yeast two-hybrid screen was performed using a human cDNA library to identify potential LASS5- interaction partners. One identified clone encodes succinate dehydrogenase subunit B (SDHB). Mammalian two-hybrid assays showed that LASS5 interacts with SDHB, and the result was also confirmed by GST pull-down and coimmunoprecipitation assays...
2016: Current Molecular Medicine
Pritam Mandal, Pakiza Noutsi, Sahraoui Chaieb
Cholesterol is crucial to the mechanical properties of cell membranes that are important to cells' behavior. Its depletion from the cell membranes could be dramatic. Among cyclodextrins (CDs), methyl beta cyclodextrin (MβCD) is the most efficient to deplete cholesterol (Chol) from biomembranes. Here, we focus on the depletion of cholesterol from a C16 ceramide/cholesterol (C16-Cer/Chol) mixed monolayer using MβCD. While the removal of cholesterol by MβCD depends on the cholesterol concentration in most mixed lipid monolayers, it does not depend very much on the concentration of cholesterol in C16-Cer/Chol monolayers...
2016: Scientific Reports
Shaghayegh Tavakoli Tabazavareh, Aaron Seitz, Peter Jernigan, Carolin Sehl, Simone Keitsch, Stephan Lang, Barbara C Kahl, Michael Edwards, Heike Grassmé, Erich Gulbins, Katrin Anne Becker
BACKGROUND: Pulmonary Staphylococcus aureus (S. aureus) infections occur early in a high percentage of cystic fibrosis (CF) patients and it is believed that these infections facilitate further colonization of CF lungs with Pseudomonas aeruginosa (P. aeruginosa). Previous studies demonstrated a marked reduction of sphingosine in tracheal and bronchial epithelial cells in CF compared to wild type mice, while ceramide is massively increased in CF mice. METHODS: We investigated the effect of C18-sphingosine and C16-ceramide on S...
2016: Cellular Physiology and Biochemistry
Rodolfo Savica, Melissa E Murray, Xuan-Mai Persson, Kejal Kantarci, Joseph E Parisi, Dennis W Dickson, Ronald C Petersen, Tanis J Ferman, Bradley F Boeve, Michelle M Mielke
INTRODUCTION: The clinical and pathological phenotypes of Dementia with Lewy Bodies (DLB) and Alzheimer's disease (AD) often overlap. We examined whether plasma lipids differed among individuals with autopsy-confirmed Lewy Body pathology or AD pathology. METHODS: We identified four groups with available plasma two years prior to death: high (n=12) and intermediate likelihood DLB (n=14) based on the third report of the DLB consortium; dementia with Alzheimer's pathology (AD; n=18); and cognitively normal with normal aging pathology (n=21)...
2016: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Elisa Fabbri, An Yang, Eleanor M Simonsick, Chee W Chia, Marco Zoli, Norman J Haughey, Michelle M Mielke, Luigi Ferrucci, Paul M Coen
Cardiorespiratory fitness (VO2 peak) declines with age and is an independent risk factor for morbidity and mortality in older adults. Identifying biomarkers of low fitness may provide insight for why some individuals experience an accelerated decline of aerobic capacity and may serve as clinically valuable prognostic indicators of cardiovascular health. We investigated the relationship between circulating ceramides and VO2 peak in 443 men and women (mean age of 69) enrolled in the Baltimore Longitudinal Study of Aging (BLSA)...
October 2016: Aging Cell
Bianca Brüggen, Christiane Kremser, Andreas Bickert, Philipp Ebel, Katharina Vom Dorp, Konrad Schultz, Peter Dörmann, Klaus Willecke, Karin Dedek
Complex sphingolipids are strongly expressed in neuronal tissue and contain ceramides in their backbone. Ceramides are synthesized by six ceramide synthases (CerS1-6). Although it is known that each tissue has a unique profile of ceramide synthase expression and ceramide synthases are implicated in several neurodegenerative disorders, the expression of ceramide synthase isoforms has not been investigated in the retina. Here we demonstrate CerS1, CerS2 and CerS4 expression in mouse retina and cornea, with CerS4 ubiquitously expressed in all retinal neurons and Müller cells...
July 2016: European Journal of Neuroscience
Nithin B Boppana, Jeremy S DeLor, Eric Van Buren, Alicja Bielawska, Jacek Bielawski, Jason S Pierce, Mladen Korbelik, Duska Separovic
We and others have shown that stresses, including photodynamic therapy (PDT), can disrupt the de novo sphingolipid biosynthesis pathway, leading to changes in the levels of sphingolipids, and subsequently, modulation of cell death. The de novo sphingolipid biosynthesis pathway includes a ceramide synthase-dependent reaction, giving rise to dihydroceramide, which is then converted in a desaturase-dependent reaction to ceramide. In this study we tested the hypothesis that combining Foscan-mediated PDT with desaturase inhibitor fenretinide (HPR) enhances cancer cell killing...
June 2016: Journal of Photochemistry and Photobiology. B, Biology
Yi Xing, Yi Tang, Lina Zhao, Qi Wang, Wei Qin, Jin-Lan Zhang, Jianping Jia
BACKGROUND: Various evidence demonstrates the influences of ceramides on Alzheimer's disease (AD) pathogenesis. Furthermore, increased ceramides were also suggested to be related to cognitive decline. However, the association between ceramides and neuropsychiatric symptoms of AD remains unclear. OBJECTIVE: This study sought to investigate the association between plasma ceramide levels and multiple neuropsychiatric symptoms in AD. METHODS: A total of 98 patients and 92 cognitively normal controls participated in this study, including 56 with mild AD and 42 with moderate to severe AD...
April 12, 2016: Journal of Alzheimer's Disease: JAD
Georgios Grammatikos, Niklas Schoell, Nerea Ferreirós, Dimitra Bon, Eva Herrmann, Harald Farnik, Verena Köberle, Albrecht Piiper, Stefan Zeuzem, Bernd Kronenberger, Oliver Waidmann, Josef Pfeilschifter
We have recently shown that major alterations of serum sphingolipid metabolites in chronic liver disease associate significantly with the stage of liver fibrosis in corresponding patients. In the current study we assessed via mass spectrometry serum concentrations of sphingolipid metabolites in a series of 122 patients with hepatocellular carcinoma (HCC) compared to an age- and sex-matched series of 127 patients with cirrhosis. We observed a highly significant upregulation of long and very long chain ceramides (C16-C24) in the serum of patients with HCC as compared to patients with cirrhosis (P < 0...
April 5, 2016: Oncotarget
Takayuki Sassa, Taisuke Hirayama, Akio Kihara
Ceramide and complex sphingolipids regulate important cellular functions including cell growth, apoptosis, and signaling. Dysregulation of sphingolipid metabolism leads to pathological consequences such as sphingolipidoses and insulin resistance. Ceramides in mammals vary greatly in their acyl-chain composition: six different ceramide synthase isozymes (CERS1-6) that exhibit distinct substrate specificity and tissue distribution account for this diversity. In the present study, we demonstrated that CERS2-6 were phosphorylated at the cytoplasmic C-terminal regions...
April 1, 2016: Journal of Biological Chemistry
Fabian Braun, Markus M Rinschen, Valerie Bartels, Peter Frommolt, Bianca Habermann, Jan H J Hoeijmakers, Björn Schumacher, Martijn E T Dollé, Roman-Ulrich Müller, Thomas Benzing, Bernhard Schermer, Christine E Kurschat
Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies...
March 2016: Aging
Dominic Gosejacob, Philipp S Jäger, Katharina Vom Dorp, Martin Frejno, Anne C Carstensen, Monika Köhnke, Joachim Degen, Peter Dörmann, Michael Hoch
Ceramides are bioactive sphingolipids, which are composed of sphingoid bases carrying acyl chains of various lengths. Ceramides are synthesized by a family of six ceramide synthases (CerS) in mammals, which produce ceramides with differentN-linked acyl chains. Increased ceramide levels are known to contribute to the development of obesity and insulin resistance. Recently, it has been demonstrated that the ceramide acylation pattern is of particular importance for an organism to maintain energy homeostasis. However, which of theCerSfamily members are involved in this process is not yet completely known...
March 25, 2016: Journal of Biological Chemistry
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