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C16 ceramide

Songhwa Choi, Justin M Snider, Nicole Olakkengil, Johana M Lambert, Andrea K Anderson, Jessica S Ross-Evans, L Ashley Cowart, Ashley J Snider
Saturated fatty acids (SFAs) have been shown to induce endoplasmic reticulum (ER) stress and chronic inflammatory responses, as well as alter sphingolipid metabolism. Disruptions in ER stress and sphingolipid metabolism have also been implicated in intestinal inflammation. Therefore, to elucidate the roles of SFAs in ER stress and inflammation in intestinal epithelial cells, we examined myristate (C14:0) and palmitate (C16:0). Myristate, but not palmitate, induced ER stress signaling, including activation of inositol-requiring enzyme 1 (IRE1) and X-box binding protein 1 (XBP1) signaling...
May 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Caroline Mota Fernandes, Gustavo H Goldman, Maurizio Del Poeta
Filamentous and dimorphic fungi cause invasive mycoses associated with high mortality rates. Among the fungal determinants involved in the establishment of infection, glycosphingolipids (GSLs) have gained increased interest in the last few decades. GSLs are ubiquitous membrane components that have been isolated from both filamentous and dimorphic species and play a crucial role in polarized growth as well as hypha-to-yeast transition. In fungi, two major classes of GSLs are found: neutral and acidic GSLs. Neutral GSLs comprise glucosylceramide and galactosylceramide, which utilize Δ4-Δ8-9-methyl-sphingadienine as a sphingoid base, linked to a C16-18 fatty acid chain, forming ceramide, and to a sugar residue, such as glucose or galactose...
May 15, 2018: MBio
Linda R Peterson, Vanessa Xanthakis, Meredith S Duncan, Stefan Gross, Nele Friedrich, Henry Völzke, Stephan B Felix, Hui Jiang, Rohini Sidhu, Matthias Nauck, Xuntian Jiang, Daniel S Ory, Marcus Dörr, Ramachandran S Vasan, Jean E Schaffer
BACKGROUND: Recent studies suggest that circulating concentrations of specific ceramide species may be associated with coronary risk and mortality. We sought to determine the relations between the most abundant plasma ceramide species of differing acyl chain lengths and the risk of coronary heart disease (CHD) and mortality in community-based samples. METHODS AND RESULTS: We developed a liquid chromatography/mass spectrometry assay to quantify plasma C24:0, C22:0, and C16:0 ceramides and ratios of these very-long-chain/long-chain ceramides in 2642 FHS (Framingham Heart Study) participants and in 3134 SHIP (Study of Health in Pomerania) participants...
May 3, 2018: Journal of the American Heart Association
Mutay Aslan, Ebru Kıraç, Sabriye Kaya, Filiz Özcan, Ozan Salim, Osman Alphan Küpesiz
Limited data are available on the serum levels of different sphingomyelin (CerPCho) and ceramide (CER) species in sickle-cell disease (SCD). This study was aimed at identifying the levels of C16-C24 CerPCho and C16-C24 CER in serum obtained from SCD patients and controls. Circulating levels of neutral sphingomyelinase (N-SMase) activity, ceramide-1-phosphate (C1P), and sphingosine-1-phosphate (S1P) were also determined. Blood was collected from 35 hemoglobin (Hb)A volunteers and 45 homozygous HbSS patients...
April 16, 2018: Lipids
Xia Gao, Katie Lee, Michael A Reid, Sydney M Sanderson, Chuping Qiu, Siqi Li, Juan Liu, Jason W Locasale
Cell proliferation can be dependent on the non-essential amino acid serine, and dietary restriction of serine inhibits tumor growth, but the underlying mechanisms remain incompletely understood. Using a metabolomics approach, we found that serine deprivation most predominantly impacts cellular acylcarnitine levels, a signature of altered mitochondrial function. Fuel utilization from fatty acid, glucose, and glutamine is affected by serine deprivation, as are mitochondrial morphological dynamics leading to increased fragmentation...
March 27, 2018: Cell Reports
Liansheng Zhong, Ji Na Kong, Michael B Dinkins, Silvia Leanhart, Zhihui Zhu, Stefka D Spassieva, Haiyan Qin, Hsuan-Pei Lin, Ahmed Elsherbini, Rebecca R Wang, Xue Jiang, Mariana Nikolova-Karakashian, Guanghu Wang, Erhard Bieberich
Sphingolipids are key signaling lipids in cancer. Genome-wide studies have identified neutral sphingomyelinase-2 (nSMase2), an enzyme generating ceramide from sphingomyelin (SM), as a potential repressor for heptocellular carcinoma. However, little is known about the sphingolipids regulated by nSMase2 and their roles in liver tumor development. We discovered growth of spontaneous liver tumors in 27.3% (9 of 33) of aged male nSMase2-deficient (fro/fro) mice. Lipidomics analysis showed marked increase of SM in the tumor...
March 22, 2018: Journal of Lipid Research
Victoria M Pak, Feng Dai, Brendan T Keenan, Nalaka S Gooneratne, Allan I Pack
Sleepiness and cardiovascular disease share common molecular pathways; thus, metabolic risk factors for sleepiness may also predict cardiovascular disease risk. Daytime sleepiness predicts mortality and cardiovascular disease, although the mechanism is unidentified. This study explored the associations between subjective sleepiness and metabolite concentrations in human blood plasma within the oxidative and inflammatory pathways, in order to identify mechanisms that may contribute to sleepiness and cardiovascular disease risk...
April 2018: Sleep Medicine
Akshaya K Meher, Michael Spinosa, John P Davis, Nicolas Pope, Victor E Laubach, Gang Su, Vlad Serbulea, Norbert Leitinger, Gorav Ailawadi, Gilbert R Upchurch
OBJECTIVE: Neutrophils promote experimental abdominal aortic aneurysm (AAA) formation via a mechanism that is independent from MMPs (matrix metalloproteinases). Recently, we reported a dominant role of IL (interleukin)-1β in the formation of murine experimental AAAs. Here, the hypothesis that IL-1β-induced neutrophil extracellular trap formation (NETosis) promotes AAA was tested. APPROACH AND RESULTS: NETs were identified through colocalized staining of neutrophil, Cit-H3 (citrullinated histone H3), and DNA, using immunohistochemistry...
April 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Kristi Helke, Peggi Angel, Ping Lu, Elizabeth Garrett-Mayer, Besim Ogretmen, Richard Drake, Christina Voelkel-Johnson
Colitis, an inflammatory disease of the digestive tract, is increasing in incidence and prevalence. Intestinal inflammation can occur as a consequence of dysfunctions in sphingolipid metabolism. In this study we used ceramide synthase 6 (CerS6) deficient mice, which have a reduced ability to generate long chain C16 -ceramide, to investigate the role of this enzyme in dextran sodium salt (DSS)-induced colitis. While CerS6-deficient mice are protected from T cell mediated colitis, in the T cell independent DSS model lack of CerS6 resulted in a more rapid onset of disease symptoms...
January 26, 2018: Scientific Reports
Gili Bisker, Naveed A Bakh, Michael A Lee, Jiyoung Ahn, Minkyung Park, Ellen B O'Connell, Nicole M Iverson, Michael S Strano
Corona phase molecular recognition (CoPhMoRe) is a technique whereby an external, adsorbed phase around a colloidal nanoparticle is selected such that its molecular conformation or interaction recognizes a specific target analyte. In this work, we employ a high-throughput screening of a library of poly(ethylene glycol) (PEG)-conjugated lipids adsorbed onto near-infrared fluorescent single-walled carbon nanotubes to discover a corona phase selective for insulin. We find that a C16 -PEG(2000 Da)-ceramide causes a 62% fluorescent intensity decrease of the (10,2) chirality nanotube in the presence of 20 μg/mL insulin...
February 23, 2018: ACS Sensors
Jérôme Becam, Tim Walter, Anne Burgert, Jan Schlegel, Markus Sauer, Jürgen Seibel, Alexandra Schubert-Unkmeir
Certain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C6 and long-chain C16 -ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) demonstrated that short-chain ceramides and a ω-azido-functionalized C6 -ceramide were active against Neisseria meningitidis and N...
December 15, 2017: Scientific Reports
Adam Dinoff, Mahwesh Saleem, Nathan Herrmann, Michelle M Mielke, Paul I Oh, Swarajya Lakshmi Vattem Venkata, Norman J Haughey, Krista L Lanctôt
Background: Depression is highly prevalent in individuals with coronary artery disease (CAD) and increases the risk of future cardiac events and mortality. Sphingolipids have been implicated in the pathophysiology of both CAD and depression. This study assessed the association between plasma sphingolipid concentrations and depressive symptoms in CAD subjects. Methods: Depressive symptoms were measured using the depression subscale of the self-reported Hospital Anxiety and Depression Scale (HADS)...
November 2017: Brain and Behavior
Kenji Mizumura, Matthew J Justice, Kelly S Schweitzer, Sheila Krishnan, Irina Bronova, Evgeny V Berdyshev, Walter C Hubbard, Yael Pewzner-Jung, Anthony H Futerman, Augustine M K Choi, Irina Petrache
The mechanisms by which lung structural cells survive toxic exposures to cigarette smoke (CS) are not well defined but may involve proper disposal of damaged mitochondria by macro-autophagy (mitophagy), processes that may be influenced by pro-apoptotic ceramide (Cer) or its precursor dihydroceramide (DHC). Human lung epithelial and endothelial cells exposed to CS exhibited mitochondrial damage, signaled by phosphatase and tensin homolog-induced putative kinase 1 (PINK1) phosphorylation, autophagy, and necroptosis...
January 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Matthew J Scheffel, Kristi Helke, Ping Lu, Jacob S Bowers, Besim Ogretmen, Elizabeth Garrett-Mayer, Chrystal M Paulos, Christina Voelkel-Johnson
Sphingolipids regulate critical cellular processes including inflammation. Ceramide, which serves a central role in sphingolipid metabolism, is generated by six ceramide synthases (CerS) that differ in substrate specificity. CerS6 preferentially generates C16 -ceramide and its mRNA is highly expressed in immune tissues. In this study we analyzed how deficiency of CerS6 impacts on the development of colitis using an adoptive transfer model. Adoptive transfer of CerS6-deficient splenocytes, which have significantly decreased levels of C16 -ceramide, showed that CerS6-deficiency protected against the development of colitis...
November 14, 2017: Scientific Reports
Loay Kh M Hassouneh, Olga A Timofiychuk, Nataliya A Babenko
Malfunction of skeletal muscles and dysregulated turnover of sphingolipids in the insulin responsive tissues have been determined at old age. Present article investigates the role of acid sphingomyelinase (SMase)-dependent ceramide accumulation in reduction of the skeletal muscle sensitivity to insulin action at old age. The 3-, 12- and 24-month-old Wistar male rats were used in the experiments. The progressive increase of ceramide content and ceramide/sphingomyeline (SM) ratio was determined in the extensor digitorum longus (EDL) muscle during aging of rats...
November 10, 2017: General Physiology and Biophysics
Adrian Paz Ramos, Gert Gooris, Joke Bouwstra, Michel Lafleur
The stratum corneum (SC), the top layer of skin, dictates the rate of both water loss through the skin and absorption of exogenous molecules into the body. The crystalline organization of the lipids in the SC is believed to be a key feature associated with the very limited permeability of the skin. In this work, we characterized the organization of SC lipid models that include, as in native SC, cholesterol, a series of FFAs (saturated with C16-C24 chains), as well as a ceramide bearing an oleate chain-linked to a very long saturated acyl chain [ N -melissoyl-oleoyloxy hexacosanoyl-D- erythro -sphingosine (Cer EOS)]...
January 2018: Journal of Lipid Research
T J Butler, D Ashford, A-M Seymour
BACKGROUND AND AIMS: Obesity and cardiac left ventricular hypertrophy (LVH) are recognised independent risk factors in the development of heart failure (HF). However, the combination of these factors may exacerbate the onset of cardiovascular disease by mechanisms as yet unclear. LVH leads to significant cellular remodelling, including alterations in metabolism which may result in an inappropriate accumulation of lipids and eventual lipotoxicity and apoptosis. The aim of the study was to determine the impact of dietary manipulation on cardiac metabolism in the obese and hypertrophied heart...
November 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Ivan U Kouzel, Gottfried Pohlentz, Julia S Schmitz, Daniel Steil, Hans-Ulrich Humpf, Helge Karch, Johannes Müthing
Shiga toxins (Stxs) released by enterohemorrhagic Escherichia coli (EHEC) into the human colon are the causative agents for fatal outcome of EHEC infections. Colon epithelial Caco-2 and HCT-8 cells are widely used for investigating Stx-mediated intestinal cytotoxicity. Only limited data are available regarding precise structures of their Stx receptor glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer), and lipid raft association. In this study we identified Gb3Cer and Gb4Cer lipoforms of serum-free cultivated Caco-2 and HCT-8 cells, chiefly harboring ceramide moieties composed of sphingosine (d18:1) and C16:0, C22:0 or C24:0/C24:1 fatty acid...
October 25, 2017: Toxins
Kyung Cheul Shin, Injae Hwang, Sung Sik Choe, Jeu Park, Yul Ji, Jong In Kim, Gha Young Lee, Sung Hee Choi, Jianhong Ching, Jean-Paul Kovalik, Jae Bum Kim
Obesity is closely associated with increased adipose tissue macrophages (ATMs), which contribute to systemic insulin resistance and altered lipid metabolism by creating a pro-inflammatory environment. Very low-density lipoprotein receptor (VLDLR) is involved in lipoprotein uptake and storage. However, whether lipid uptake via VLDLR in macrophages affects obesity-induced inflammatory responses and insulin resistance is not well understood. Here we show that elevated VLDLR expression in ATMs promotes adipose tissue inflammation and glucose intolerance in obese mice...
October 20, 2017: Nature Communications
Nadejda V Pavlova, Su-Chen Li, Yu-Teh Li
The hepatopancreas of oyster, Crassostrea virginica, was found to contain two unique glycosphingolipid (GSL) cleaving enzymes, ceramide glycanase (CGase) and ceramidase. These two enzymes were found to be tightly associated together through the consecutive purification steps including gel filtration, hydrophobic interaction and cation-exchange chromatographies. They were separated only by preparatory SDS-PAGE. The purified CGase was found to have a molecular mass of 52 kDa and pH optimum of 3.2-3.3. This enzyme prefers to hydrolyze the acidic GSLs, II3 SO3 LacCer and gangliosides over the neutral GSLs...
February 2018: Glycoconjugate Journal
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