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https://www.readbyqxmd.com/read/29702255/the-role-of-sphingolipid-metabolism-disruption-on-lipopolysaccharide-induced-lung-injury-in-mice
#1
Renata Tiemi Okuro, Mariana Nascimento Machado, Natália Vasconcelos Casquilho, Alcendino Jardim-Neto, Alysson Roncally-Carvalho, Georgia Correa Atella, Walter Araujo Zin
AIM: This study assessed pulmonary outcomes generated by inhibiting key enzymes of sphingolipid metabolism pathways related to ceramide synthesis in a murine model of lung injury induced by lipopolysaccharide (LPS). METHODS: C57BL/6 male adult mice received LPS intratracheally and the expressions of acid sphingomyelinase (ASM), neutral sphingomyelinase (NSM), serine palmitoyl transferase (SPT) and dihydroceramide synthase (DS) were assessed at 2, 4, 6, 12 and 24 h after LPS instillation in lung homogenate (n = 30)...
April 24, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29509438/quantifying-ceramide-kinetics-in-vivo-using-stable-isotope-tracers-and-lc-ms-ms
#2
Ying Chen, Olga Berejnaia, Jinqi Liu, Sheng-Ping Wang, Natalie A Daurio, Wu Yin, Rafael Mayoral, Aleksandr Petrov, Takhar Kasumov, Guo-Fang Zhang, Stephen F Previs, David E Kelley, David G McLaren
Numerous studies have implicated dyslipidemia as a key factor in mediating insulin resistance. Ceramides have received special attention since their levels are inversely associated with normal insulin signaling and positively associated with factors that are involved in cardiometabolic disease. Despite the growing literature surrounding ceramide biology, there are limited data regarding the activity of ceramide synthesis and turnover in vivo. Herein, we demonstrate the ability to measure ceramide kinetics by coupling the administration of [2 H]water with LC-MS/MS analyses...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29474492/docosahexaenoic-acid-antagonizes-the-boosting-effect-of-palmitic-acid-on-lps-inflammatory-signaling-by-inhibiting-gene-transcription-and-ceramide-synthesis
#3
Junfei Jin, Zhongyang Lu, Yanchun Li, L Ashley Cowart, Maria F Lopes-Virella, Yan Huang
It is well known that saturated fatty acids (SFAs) and unsaturated fatty acid, in particular omega-3 polyunsaturated fatty acids (n-3 PUFAs), have different effects on inflammatory signaling: SFAs are pro-inflammatory but n-3 PUFAs have strong anti-inflammatory properties. We have reported that palmitic acid (PA), a saturated fatty acid, robustly amplifies lipopolysaccharide (LPS) signaling to upregulate proinflammatory gene expression in macrophages. We also reported that the increased production of ceramide (CER) via sphingomyelin (SM) hydrolysis and CER de novo synthesis plays a key role in the synergistic effect of LPS and PA on proinflammatory gene expression...
2018: PloS One
https://www.readbyqxmd.com/read/29395144/hot-topic-ceramide-inhibits-insulin-sensitivity-in-primary-bovine-adipocytes
#4
J E Rico, W A Myers, D J Laub, A N Davis, Q Zeng, J W McFadden
In nonruminants, the sphingolipid ceramide inhibits insulin sensitivity by inactivating protein kinase B (AKT) within the insulin-signaling pathway. We have established that ceramide accrual develops with impaired systemic insulin action in ruminants during the transition from gestation to lactation, dietary palmitic acid supplementation, or controlled nutrient restriction. We hypothesized that ceramide promotes AKT inactivation and antagonizes insulin sensitivity in primary bovine adipocytes. Stromal-vascular cells were grown from bovine adipose tissue explants and cultured in differentiation media...
April 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29317528/sphingolipids-activate-the-endoplasmic-reticulum-stress-surveillance-pathway
#5
Francisco Piña, Fumi Yagisawa, Keisuke Obara, J D Gregerson, Akio Kihara, Maho Niwa
Proper inheritance of functional organelles is vital to cell survival. In the budding yeast, Saccharomyces cerevisiae , the endoplasmic reticulum (ER) stress surveillance (ERSU) pathway ensures that daughter cells inherit a functional ER. Here, we show that the ERSU pathway is activated by phytosphingosine (PHS), an early biosynthetic sphingolipid. Multiple lines of evidence support this: (1) Reducing PHS levels with myriocin diminishes the ability of cells to induce ERSU phenotypes. (2) Aureobasidin A treatment, which blocks conversion of early intermediates to downstream complex sphingolipids, induces ERSU...
February 5, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29282820/ergosterol-is-mainly-located-in-the-cytoplasmic-leaflet-of-the-yeast-plasma-membrane
#6
Lukasz M Solanko, David P Sullivan, Yves Y Sere, Maria Szomek, Anita Lunding, Katarzyna A Solanko, Azra Pizovic, Lyubomir D Stanchev, Thomas Günther Pomorski, Anant K Menon, Daniel Wüstner
Transbilayer lipid asymmetry is a fundamental characteristic of the eukaryotic cell plasma membrane (PM). While PM phospholipid asymmetry is well documented, the transbilayer distribution of PM sterols such as mammalian cholesterol and yeast ergosterol is not reliably known. We now report that sterols are asymmetrically distributed across the yeast PM, with the majority (~80%) located in the cytoplasmic leaflet. By exploiting the sterol-auxotrophic hem1Δ yeast strain we obtained cells in which endogenous ergosterol was quantitatively replaced with dehydroergosterol (DHE), a closely related fluorescent sterol that functionally and accurately substitutes for ergosterol in vivo...
March 2018: Traffic
https://www.readbyqxmd.com/read/29273450/helicobacter-pylori-depletes-cholesterol-in-gastric-glands-to-prevent-interferon-gamma-signaling-and-escape-the-inflammatory-response
#7
Pau Morey, Lennart Pfannkuch, Ervinna Pang, Francesco Boccellato, Michael Sigal, Aki Imai-Matsushima, Victoria Dyer, Manuel Koch, Hans-Joachim Mollenkopf, Philipp Schlaermann, Thomas F Meyer
BACKGROUND & AIMS: Despite inducing an inflammatory response, Helicobacter pylori can persist in the gastric mucosa for decades. H pylori expression of cholesterol-α-glucosyltransferase (encoded by cgt) is required for gastric colonization and T-cell activation. We investigated how cgt affects gastric epithelial cells and the host immune response. METHODS: MKN45 gastric epithelial cells, AGS cells, and human primary gastric epithelial cells (obtained from patients undergoing gastrectomy or sleeve resection or gastric antral organoids) were incubated with interferon gamma (IFNG) or IFNB and exposed to H pylori, including cagPAI and cgt mutant strains...
December 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29234684/changes-in-the-diaphragm-lipid-content-after-administration-of-streptozotocin-and-high-fat-diet-regime
#8
Bartlomiej Lukaszuk, Agnieszka Miklosz, Malgorzata Zendzian-Piotrowska, Beata Wojcik, Jan Gorski, Adrian Chabowski
The diaphragm is a dome-shaped skeletal muscle indispensable for breathing. Its activity contributes up to 70% of the total ventilatory function at rest. In comparison to other skeletal muscles, it is distinguished by an oxidative phenotype and uninterrupted cyclic contraction pattern. Surprisingly, the research regarding diaphragm diabetic phenotype particularly in the light of lipid-induced insulin resistance is virtually nonexistent. Male Wistar rats were randomly allocated into 3 groups: control, streptozotocin-induced (STZ) type-1 diabetes, and rodents fed with high-fat diet (HFD)...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29233519/inhibition-of-central-de-novo-ceramide-synthesis-restores-insulin-signaling-in-hypothalamus-and-enhances-%C3%AE-cell-function-of-obese-zucker-rats
#9
Mélanie Campana, Lara Bellini, Claude Rouch, Latif Rachdi, Nicolas Coant, Noémie Butin, Cécile L Bandet, Erwann Philippe, Kelly Meneyrol, Nadim Kassis, Julien Dairou, Eric Hajduch, Benoit Colsch, Christophe Magnan, Hervé Le Stunff
OBJECTIVES: Hypothalamic lipotoxicity has been shown to induce central insulin resistance and dysregulation of glucose homeostasis; nevertheless, elucidation of the regulatory mechanisms remains incomplete. Here, we aimed to determine the role of de novo ceramide synthesis in hypothalamus on the onset of central insulin resistance and the dysregulation of glucose homeostasis induced by obesity. METHODS: Hypothalamic GT1-7 neuronal cells were treated with palmitate...
February 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29157818/biological-characteristics-bioactive-components-and-antineoplastic-properties-of-sporoderm-broken-spores-from-wild-cordyceps-cicadae
#10
Yanfang Sun, Michael Wink, Pan Wang, Hongfei Lu, Hongxin Zhao, Hongtao Liu, Shixian Wang, Yang Sun, Zongsuo Liang
BACKGROUND: Cordyceps cicadae, an entomogenous fungus has been used as a dietary therapeutic in traditional Chinese medicine for several millennia, in the form of powders and decoction. However, wild C. cicadae is notably scarce. To date, there is still a lack of comprehensive and deep studies on the biological characteristics, chemical profiles and antineoplastic mechanisms of C. cicadae, especially its spores. AIM OF THE STUDY: This study aimed to identify wild C...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29092960/quantification-of-3-ketodihydrosphingosine-using-hplc-esi-ms-ms-to-study-spt-activity-in-yeast-saccharomyces-cerevisiae
#11
Jihui Ren, Justin Snider, Michael V Airola, Aaron Zhong, Nadia A Rana, Lina M Obeid, Yusuf A Hannun
Serine palmitoyltransferase (SPT) catalyzes the rate-limiting step of condensation of L-serine and palmitoyl-CoA to form 3-ketodihydrosphingosine (3KDS). Here, we report a HPLC-ESI-MS/MS method to directly quantify 3KDS generated by SPT. With this technique, we were able to detect 3KDS at a level comparable to that of dihydrosphingosine in yeast Saccharomyces cerevisiae An in vitro SPT assay measuring the incorporation of deuterated serine into deuterated 3KDS was developed. The results show that SPT kinetics in response to palmitoyl-CoA fit into an allosteric sigmoidal model, suggesting the existence of more than one palmitoyl-CoA binding site on yeast SPT and positive cooperativity between them...
January 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29025713/neutrophil-elastase-increases-airway-ceramide-levels-via-upregulation-of-serine-palmitoyltransferase
#12
Sophia Karandashova, Apparao B Kummarapurugu, Shuo Zheng, Charles E Chalfant, Judith A Voynow
Altered sphingolipid metabolism is associated with increased inflammation; however, the impact of inflammatory mediators, including neutrophil elastase (NE), on airway sphingolipid homeostasis remains unknown. Using a well-characterized mouse model of NE oropharyngeal aspiration, we investigated a potential link between NE-induced airway inflammation and increased synthesis of various classes of sphingolipids, including ceramide species. Sphingolipids in bronchoalveolar lavage fluids (BAL) were identified and quantified using reverse-phase high-performance liquid chromatography/electrospray ionization tandem mass spectrometry analysis...
January 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28857357/aspergillus-nidulans-baph-is-a-rab11-effector-that-connects-membranes-in-the-spitzenk%C3%A3-rper-with-basal-autophagy
#13
Mario Pinar, Miguel A Peñalva
Using affinity chromatography we identified the Aspergillus nidulans F-BAR-and-PH domain-containing protein BapH as a RabERAB11 effector. BapH localizes to the Spitzenkörper (SPK) in an F-actin- and Sec7-dependent manner, becoming cytosolic after inactivation of Trs120 in TRAPPII, the oligomeric GEF for RabERAB11 . Therefore, RabERAB11 contributes to the recruitment of BapH to secretory vesicles in vivo. BapH has a close homologue, SlmA, which is related to yeast Slm1p/Slm2p, localizes to eisosomes and does not bind RabERAB11 ...
November 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28714922/application-of-an-improved-hplc-fl-method-to-screen-serine-palmitoyl-transferase-inhibitors
#14
Simone Bertini, Giuseppe Saccomanni, Sara Del Carlo, Maria Digiacomo, Claudia Gargini, Ilaria Piano, Giuseppe Matteo Campisi, Riccardo Ghidoni, Marco Macchia, Clementina Manera
In this work, we reported the application and validation of an improved high-performance liquid chromatography method coupled with a fluorimetric detector (HPLC-FL) to screen the activity of two heterocyclic derivatives reported as serine palmitoyl transferase (SPT) inhibitors. The analytical conditions were optimized in terms of the derivatization procedure, chromatographic condition, extraction procedure, and method validation according to EMEA guidelines. Once fully optimized, the method was applied to assess the SPT-inhibitory activity of the above-mentioned derivatives and of the reference inhibitor myriocin...
July 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28699686/ablation-of-ceramide-synthase-2-exacerbates-dextran-sodium-sulphate-induced-colitis-in-mice-due-to-increased-intestinal-permeability
#15
Ye-Ryung Kim, Giora Volpert, Kyong-Oh Shin, So-Yeon Kim, Sun-Hye Shin, Younghay Lee, Sun Hee Sung, Yong-Moon Lee, Jung-Hyuck Ahn, Yael Pewzner-Jung, Woo-Jae Park, Anthony H Futerman, Joo-Won Park
Ceramides mediate crucial cellular processes including cell death and inflammation and have recently been implicated in inflammatory bowel disease. Ceramides consist of a sphingoid long-chain base to which fatty acids of various length can be attached. We now investigate the effect of alerting the ceramide acyl chain length on a mouse model of colitis. Ceramide synthase (CerS) 2 null mice, which lack very-long acyl chain ceramides with concomitant increase of long chain bases and C16-ceramides, were more susceptible to dextran sodium sulphate-induced colitis, and their survival rate was markedly decreased compared with that of wild-type littermates...
December 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28679588/adipocyte-mtorc1-deficiency-promotes-adipose-tissue-inflammation-and-nlrp3-inflammasome-activation-via-oxidative-stress-and-de-novo-ceramide-synthesis
#16
Patricia Chimin, Maynara L Andrade, Thiago Belchior, Vivian A Paschoal, Juliana Magdalon, Alex S Yamashita, Érique Castro, Angela Castoldi, Adriano B Chaves-Filho, Marcos Y Yoshinaga, Sayuri Miyamoto, Niels O Câmara, William T Festuccia
Mechanistic target of rapamycin complex (mTORC)1 activity is increased in adipose tissue of obese insulin-resistant mice, but its role in the regulation of tissue inflammation is unknown. Herein, we investigated the effects of adipocyte mTORC1 deficiency on adipose tissue inflammation and glucose homeostasis. For this, mice with adipocyte raptor deletion and controls fed a chow or a high-fat diet were evaluated for body mass, adiposity, glucose homeostasis, and adipose tissue inflammation. Despite reducing adiposity, adipocyte mTORC1 deficiency promoted hepatic steatosis, insulin resistance, and adipose tissue inflammation (increased infiltration of macrophages, neutrophils, and B lymphocytes; crown-like structure density; TNF-α, interleukin (IL)-6, and monocyte chemoattractant protein 1 expression; IL-1β protein content; lipid peroxidation; and de novo ceramide synthesis)...
September 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28674344/total-synthesis-of-sphingofungin-e-and-4-5-di-epi-sphingofungin-e
#17
Narumi Noda, Hisanori Nambu, Tomoya Fujiwara, Takayuki Yakura
Total synthesis of sphingofungin E and 4,5-di-epi-sphingofungin E was achieved from an intermediate same as that of myriocin and mycestericin D via antipodal stereoselective dihydroxylations.
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28621883/determination-of-the-serine-palmitoyl-transferase-inhibitor-myriocin-by-electrospray-and-q-trap-mass-spectrometry
#18
Giuseppe Matteo Campisi, Paola Signorelli, Jessica Rizzo, Claudio Ghilardi, Jacopo Antognetti, Anna Caretti, Jelena S Lazarević, Enrica Strettoi, Elena Novelli, Riccardo Ghidoni, Federico Maria Rubino, Rita Paroni
Myriocin is a potent inhibitor of serine-palmitoyl-transferase, the first and rate-determining enzyme in the sphingolipids biosynthetic pathway. This study developed, validated and applied a LC-MS/MS method to measure myriocin in minute specimens of animal tissue. The chemical analog 14-OH-myriocin was used as the internal standard. The two molecules were extracted from the tissue homogenate by solid-phase extraction, separated by gradient reversed-phase liquid chromatography and measured by negative ion electrospray mass spectrometry in the triple quadrupole...
December 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28600071/synthetic-antimicrobial-peptides-of-the-halictines-family-disturb-the-membrane-integrity-of-candida-cells
#19
Marie Kodedová, Hana Sychrová
We compared the potency of four derivatives of the antimicrobial peptide halictine-2 against six Candida species. Observed activity was peptide and species specific. Halictines rapidly permeabilized cell membranes and caused the leakage of cytosolic components. Their killing potential was enhanced by the commercial antimicrobial agent octenidine dihydrochloride. The effect on C. glabrata cells did not depend on the activity of Cdr pumps, but was influenced by their lipid composition. The pre-treatment of cells with myriocin, an inhibitor of sphingolipid synthesis, enhanced the peptides' activity, whereas pre-treatment with terbinafine and fluconazole, inhibitors of sterol synthesis, significantly weakened their efficacy...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28531105/high-mobility-group-box-1-disrupts-metabolic-function-with-cigarette-smoke-exposure-in-a-ceramide-dependent-manner
#20
Oliver J Taylor, Mikayla O Thatcher, Sheryl T Carr, Jonathan L Gibbs, Annie M Trumbull, Mitchell E Harrison, Duane R Winden, Mackenzie J Pearson, Trevor S Tippetts, William L Holland, Paul R Reynolds, Benjamin T Bikman
We have previously found that cigarette smoke disrupts metabolic function, in part, by increasing muscle ceramide accrual. To further our understanding of this, we sought to determine the role of the cytokine high-mobility group box 1 (HMGB1), which is increased with smoke exposure, in smoke-induced muscle metabolic perturbations. To test this theory, we determined HMGB1 from lungs of human smokers, as well as from lung cells from mice exposed to cigarette smoke. We also treated cells and mice directly with HMGB1, in the presence or absence of myriocin, an inhibitor of serine palmitoyltransferase, the rate-limiting enzyme in ceramide biosynthesis...
May 20, 2017: International Journal of Molecular Sciences
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