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C16 ceramide

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...
February 22, 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 Ali Bakh, Michael A Lee, Jiyoung Ahn, Minkyung Park, Ellen B O'Connell, Nicole 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(2000kDa)-Ceramide causes a 62% fluorescent intensity decrease of the (10,2) chirality nanotube in 20 µg/ml insulin concentration...
January 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 both the rate of 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 free fatty acid series (saturated with C16-C24 chains), as well as a ceramide bearing an oleate linked to a very long saturated acyl chain (Cer EOS)...
November 1, 2017: 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...
September 7, 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, II(3)SO3LacCer and gangliosides over the neutral GSLs...
October 16, 2017: Glycoconjugate Journal
Markus Blaess, Nelly Bibak, Ralf A Claus, Matthias Kohl, Gabriel A Bonaterra, Ralf Kinscherf, Stefan Laufer, Hans-Peter Deigner
Ceramide generation is involved in signal transduction of cellular stress response, in particular during stress-induced apoptosis in response to stimuli such as minimally modified Low-density lipoproteins, TNFalpha and exogenous C6-ceramide. In this paper we describe 48 diverse synthetic products and evaluate their lysosomotropic and acid sphingomyelinase inhibiting activities in macrophages. A stimuli-induced increase of C16-ceramide in macrophages can be almost completely suppressed by representative compound NB 06 providing an effective protection of macrophages against apoptosis...
September 21, 2017: European Journal of Medicinal Chemistry
Jacqueline Stöckli, Kelsey H Fisher-Wellman, Rima Chaudhuri, Xiao-Yi Zeng, Daniel J Fazakerley, Christopher C Meoli, Kristen C Thomas, Nolan J Hoffman, Salvatore P Mangiafico, Chrysovalantou E Xirouchaki, Chieh-Hsin Yang, Olga Ilkayeva, Kari Wong, Gregory J Cooney, Sofianos Andrikopoulos, Deborah M Muoio, David E James
Insulin resistance is a major risk factor for many diseases. However, its underlying mechanism remains unclear in part because it is triggered by a complex relationship between multiple factors, including genes and the environment. Here, we used metabolomics combined with computational methods to identify factors that classified insulin resistance across individual mice derived from three different mouse strains fed two different diets. Three inbred ILSXISS strains were fed high-fat or chow diets and subjected to metabolic phenotyping and metabolomics analysis of skeletal muscle...
November 24, 2017: Journal of Biological Chemistry
Myoung Jin Oh, Young Hoon Cho, So Yoon Cha, Eun Ok Lee, Jin Wook Kim, Sun Ki Kim, Chang Seo Park
Ceramides in the human stratum corneum (SC) are a mixture of diverse N-acylated fatty acids (FAs) with different chain lengths. C24 is the major class of FAs of ceramides. However, there are also other classes of ceramides with diverse chain lengths of FAs, and these lengths generally range from C16 to C26. This study aimed to prepare several types of phytoceramide containing diverse chain lengths of N-acylated FAs and compare them with C18-ceramide N-stearoyl phytosphingosine (NP) in terms of their effects on the physiological properties of the SC...
2017: Clinical, Cosmetic and Investigational Dermatology
Alexandra M V Wennberg, Marissa J Schafer, Nathan K LeBrasseur, Rodolfo Savica, Hai H Bui, Clinton E Hagen, John H Hollman, Ronald C Petersen, Michelle M Mielke
Background: Disrupted gait has been associated with an increased risk of frailty, disability, and death, but the causal molecular pathways are not well understood. Sphingolipids, including ceramides, are associated with multiple age-related diseases. Ceramides promote atrophy, necrosis, and proteolysis in cellular and animal models, and ceramide C16:0 levels are negatively correlated with muscle mass in men. However, there is a paucity of evidence examining sphingolipids and physical function...
July 25, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Jin Ook Chung, Christina Koutsari, Agnieszka Urszula Blachnio-Zabielska, Kazanna C Hames, Michael D Jensen
We investigated the effects of meal ingestion on intramyofibrillar (IMF) and subsarcolemmal (SS) ceramide metabolism in volunteers ranging from lean to obese. Thirty-eight women and men underwent a steady-state meal ingestion protocol that included a 6.5 h infusion of [U-(13)C] palmitate and muscle biopsies 1.5 h and 6.5 h after starting the tracer infusion. We measured IMF and SS sphingolipid concentrations and the contribution of plasma palmitate to intramyocellular C16:0 ceramide using LC\MS\MS. In response to meal ingestion SS C24 ceramide concentrations, but not C14-C20 concentrations, increased significantly...
September 26, 2017: American Journal of Physiology. Endocrinology and Metabolism
Efrem N Tessema, Tsige Gebre-Mariam, Stefan Lange, Bodo Dobner, Reinhard H H Neubert
The impaired epidermal barrier and skin dryness in chronic skin conditions such as atopic dermatitis, psoriasis and aged skin are associated with the depletion of ceramides (CERs) in the stratum corneum. Previously, the beneficial effects of phyto-CERs, mainly from wheat and rice, in replenishing the depleted epidermal CERs and restoring the skin barrier have been shown. However, very few efforts have been made to exploit CERs from other plants for dermal applications. In an attempt to explore alternative plant source of CERs, glucosylceramides (GlcCERs) were isolated from the lipid extract of Ethiopian oat grain (Avena abyssinica)...
October 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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