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Sphingolipids

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https://www.readbyqxmd.com/read/28527370/atherosclerotic-dyslipidemia-revealed-by-plasma-lipidomics-on-apoe-mice-fed-a-high-fat-diet
#1
Yanyan Chen, Shiyuan Wen, Miaomiao Jiang, Yan Zhu, Liqin Ding, Hong Shi, Pengzhi Dong, Jing Yang, Yue Yang
BACKGROUND AND AIMS: The pathological process of atherosclerosis is closely related to lipid accumulation at arterial wall caused by lipoproteins transporting lipids through blood. In this study, we investigate the lipid composition in the plasma of apolipoprotein E deficient (ApoE(-/-)) mice fed a high-fat diet to reveal atherosclerosis-induced dyslipidemia. METHODS: ApoE(-/-) and corresponding wild-type C57BL/6J mice were used as the pathology model and control, respectively, and were fed a high-fat or normal diet...
May 11, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28526017/the-effect-of-hypoxia-on-the-lipidome-of-recombinant-pichia-pastoris
#2
Núria Adelantado, Pablo Tarazona, Karlheinz Grillitsch, Xavier García-Ortega, Sergi Monforte, Francisco Valero, Ivo Feussner, Günther Daum, Pau Ferrer
BACKGROUND: Cultivation of recombinant Pichia pastoris (Komagataella sp.) under hypoxic conditions has a strong positive effect on specific productivity when the glycolytic GAP promoter is used for recombinant protein expression, mainly due to upregulation of glycolytic conditions. In addition, transcriptomic analyses of hypoxic P. pastoris pointed out important regulation of lipid metabolism and unfolded protein response (UPR). Notably, UPR that plays a role in the regulation of lipid metabolism, amino acid metabolism and protein secretion, was found to be upregulated under hypoxia...
May 19, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28524744/sphingosine-1-phosphate-signaling-in-bone-remodeling-multifaceted-roles-and-therapeutic-potential
#3
Anastasia Meshcheryakova, Diana Mechtcheriakova, Peter Pietschmann
Sphingolipids belong to a complex class of lipid molecules that are crucially involved in the regulation of important biological processes including proliferation, migration and apoptosis. Given the significant progress made in understanding the sphingolipid pathobiology of several diseases, sphingolipid-related checkpoints emerge as attractive targets. Recent data indicate the multifaceted contribution of the sphingolipid machinery to osteoclast - osteoblast crosstalk, representing one of the pivotal interactions underlying bone homeostasis...
May 19, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28521610/sphk1-sphingosine-kinase-1-induces-epithelial-mesenchymal-transition-by-promoting-the-autophagy-linked-lysosomal-degradation-of-cdh1-e-cadherin-in-hepatoma-cells
#4
Hong Liu, Yan Ma, Hong-Wei He, Wu-Li Zhao, Rong-Guang Shao
SPHK1 (sphingosine kinase 1), a regulator of sphingolipid metabolites, plays a causal role in the development of hepatocellular carcinoma (HCC) through augmenting HCC invasion and metastasis. However, the mechanism by which SPHK1 signaling promotes invasion and metastasis in HCC remains to be clarified. Here, we reported that SPHK1 induced the epithelial-mesenchymal transition (EMT) by accelerating CDH1/E-cadherin lysosomal degradation and facilitating the invasion and metastasis of HepG2 cells. Initially, we found that SPHK1 promoted cell migration and invasion and induced the EMT process through decreasing the expression of CDH1, which is an epithelial marker...
May 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28516428/cerebrovascular-angiogenic-reprogramming-upon-lrp1-repression-impact-on-sphingosine-1-phosphate-mediated-signaling-in-brain-endothelial-cell-chemotactism
#5
Amélie Vézina, Cyndia Charfi, Alain Zgheib, Borhane Annabi
Switches in sphingolipid metabolism have recently been associated with oncogenic transformation, and a role for the low-density lipoprotein receptor-related protein 1 (LRP1) in sphingosine-1-phosphate (S1P) proangiogenic signaling inferred. S1P signaling crosstalk with LRP1 in brain microvascular endothelial cells (HBMEC) is however unclear. Transient in vitro siLRP1 gene silencing was compared to stable shLRP1 knockdown. We observed decreased expression of CCAAT/enhancer binding protein β (C/EBPβ), a transcription factor for which multiple binding sites are found within the promoter sequences of all five S1P receptor members, upon stable but not transient LRP1 repression...
May 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28515456/metabolomic-analysis-shows-differential-hepatic-effects-of-t2-and-t3-in-rats-after-short-term-feeding-with-high-fat-diet
#6
Liliana F Iannucci, Federica Cioffi, Rosalba Senese, Fernando Goglia, Antonia Lanni, Paul M Yen, Rohit A Sinha
Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T2 and T3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515139/changes-in-ceramide-metabolism-are-essential-in-madin-darby-canine-kidney-cell-differentiation
#7
Lucila Gisele Pescio, Bruno Jaime Santacreu, Vanina Gisela Lopez, Carlos Humberto Paván, Daniela Judith Romero, Nicolás Octavio Favale, Norma Beatriz Sterin-Speziale
Ceramides and complex sphingolipids with defined acyl-chain lengths play important roles in numerous cell processes. Six ceramide synthase isoenzymes (CerS1-6) are the key enzymes responsible for the production of the diversity of molecular species. In this study, we investigated the changes in sphingolipid metabolism during the differentiation of Madin-Darby Canine Kidney (MDCK) cells. By MALDI TOF TOF MS, we analyzed the molecular species of ceramide (Cer), glucosylceramide (GlcCer), lactosylceramide (LacCer) and sphingomyelin (SM) in non-differentiated and differentiated cells (cultured under hypertonicity)...
May 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28510438/complex-effects-of-24-1-sphingolipids-in-membranes-containing-dioleoyl-phosphatidylcholine-and-cholesterol
#8
Aritz B Garcia-Arribas, Emilio J Gonzalez-Ramirez, Jesús Sot, Itziar Areso, Alicia Alonso, Felix M Goni
The effects of C24:1 sphingolipids have been tested in phospholipid bilayers containing cholesterol. Confocal microscopy, differential scanning calorimetry, and atomic force microscopy imaging and force curves have been used. More precisely, the effects of C24:1 ceramide (nervonoyl ceramide, nCer) were evaluated and compared to those of C16:0 ceramide (palmitoyl ceramide, pCer) in bilayers composed basically of dioleoyl phosphatidylcholine, sphingomyelin (either C24:1, nSM or C16:0, pSM) and cholesterol. Combination of equimolecular amounts of C24:1 and C16:0 sphingolipids were also studied under the same conditions...
May 16, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28507162/lipophagy-prevents-activity-dependent-neurodegeneration-due-to-dihydroceramide-accumulation-in-vivo
#9
Wei-Hung Jung, Chung-Chih Liu, Yu-Lian Yu, Yu-Chin Chang, Wen-Yu Lien, Hsi-Chun Chao, Shu-Yi Huang, Ching-Hua Kuo, Han-Chen Ho, Chih-Chiang Chan
Dihydroceramide desaturases are evolutionarily conserved enzymes that convert dihydroceramide (dhCer) to ceramide (Cer). While elevated Cer levels cause neurodegenerative diseases, the neuronal activity of its direct precursor, dhCer, remains unclear. We show that knockout of the fly dhCer desaturase gene, infertile crescent (ifc), results in larval lethality with increased dhCer and decreased Cer levels. Light stimulation leads to ROS increase and apoptotic cell death in ifc-KO photoreceptors, resulting in activity-dependent neurodegeneration...
May 15, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28502799/proteomics-and-metabolomics-driven-pathway-reconstruction-of-mung-bean-for-nutraceutical-evaluation
#10
Akiko Hashiguchi, Wei Zhu, Jingkui Tian, Setsuko Komatsu
Mung bean is a legume crop which has a various health-promoting effects. Although rich flavonoids are reported to be responsible for its biological activities, little is known about other nutrients that may potentiate the activities. To obtain information on mung bean nutritional properties, gel-free/label-free proteomic analysis and metabolomic profiling were combined. Pathway reconstruction detected that amino acid metabolism is more active in flesh. Coat contained wider variety of lipids and phenolic acids/flavonoids than flesh...
May 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28500264/s1p1-mediated-anti-ras-cardioprotection-pivotal-role-of-mast-cell-aldh2
#11
Alice Marino, Takuya Sakamoto, Pablo A Robador, Kengo Tomita, Roberto Levi
In the ischemic-reperfused (I/R) heart, renin-containing mast cells (MC) release enzymatically active renin, activating a local renin-angiotensin system (RAS), causing excessive norepinephrine release and arrhythmic dysfunction. Activation of Gi-receptors on MC, and/or ischemic preconditioning (IPC), prevent renin release, thus providing anti-RAS cardioprotection. We questioned whether sphingosine-1-phosphate (S1P), a sphingolipid produced in the I/R heart, might afford anti-RAS cardioprotection by activating Gi-coupled S1P1 receptors (S1P1R) on MC...
May 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28499696/fenofibrate-decreases-plasma-ceramide-in-type-2-diabetes-patients-a-novel-marker-of-cvd
#12
M Croyal, Z Kaabia, L León, S Ramin-Mangata, T Baty, F Fall, S Billon-Crossouard, A Aguesse, T Hollstein, D R Sullivan, E Nobecourt, G Lambert, M Krempf
AIM: The benefit of the lipid-lowering drug fenofibrate on cardiovascular outcomes is controversial. Our aim was to find new circulating markers to identify those patients most likely to benefit from fenofibrate prescription. METHODS: Analyses were conducted of plasma samples collected from 102 patients with type 2 diabetes, enrolled in the FIELD trial, before and after fenofibrate treatment (200mg/day). Non-targeted and targeted lipid analyses and apolipoprotein measurements were made using mass spectrometry methods...
May 9, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28497335/methods-for-analyzing-sphingosine-1-phosphate-signaling-in-human-and-mouse-primary-mast-cells
#13
Alena P Chumanevich, Piper A Wedman, Carole A Oskeritzian
Mast cells produce a potently bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) constitutively and upon activation. The ligation of S1P to its type 2 receptor on mast cells triggers a novel downstream signaling pathway that we discovered links activation of transcription factor signal transducer and activator of transcription 3 to mast cell-derived chemokine release in both humans and mice. In this chapter, we describe the methods used to study S1P signaling in human and mouse primary mast cells...
May 12, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28495678/sphingolipid-metabolic-flow-controls-phosphoinositide-turnover-at-the-trans-golgi-network
#14
Serena Capasso, Lucia Sticco, Riccardo Rizzo, Marinella Pirozzi, Domenico Russo, Nina A Dathan, Felix Campelo, Josse van Galen, Maarit Hölttä-Vuori, Gabriele Turacchio, Angelika Hausser, Vivek Malhotra, Isabelle Riezman, Howard Riezman, Elina Ikonen, Chiara Luberto, Seetharaman Parashuraman, Alberto Luini, Giovanni D'Angelo
Sphingolipids are membrane lipids globally required for eukaryotic life. The sphingolipid content varies among endomembranes with pre- and post-Golgi compartments being poor and rich in sphingolipids, respectively. Due to this different sphingolipid content, pre- and post-Golgi membranes serve different cellular functions. The basis for maintaining distinct subcellular sphingolipid levels in the presence of membrane trafficking and metabolic fluxes is only partially understood. Here, we describe a homeostatic regulatory circuit that controls sphingolipid levels at the trans-Golgi network (TGN)...
May 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28495476/studies-on-diagnostic-biomarkers-and-therapeutic-mechanism-of-alzheimer-s-disease-through-metabolomics-and-hippocampal-proteomics
#15
Weiwei Lin, Jianmei Zhang, Yanmeng Liu, Ruijun Wu, Haisong Yang, Xiaobo Hu, Xiaomei Ling
Alzheimer's disease (AD) is the main cause of dementia, but precise diagnosis and treatment are not sufficient so far. The purpose of this study is to develop biomarkers and therapeutic targets for diagnosis and better understanding of AD. As a result, lysophosphatidylcholine and intermediates of sphingolipid metabolism including sphinganine-1-phosphate, sphingosine-1-phosphate, sphingomyelin, and sphingosine in plasma were annotated as potential biomarkers by using UPLC-Q-TOF-MS and UHPLC-Q-Exactive-MS. Besides, glutathione S-transferases (GSTs) including GstA3, Gstm1, Gstm5, Gstm3, Gstk1 and Gstp1 were significantly enhanced in AD hippocampus by using label free nano-LC-MS/MS...
May 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28494460/persistently-altered-metabolic-phenotype-following-perinatal-excitotoxic-brain-injury
#16
Benjamin J Blaise, Leslie Schwendimann, Vibol Chhor, Vincent Degos, Mark P Hodson, Guido Dallmann, Matthias Keller, Pierre Gressens, Bobbi Fleiss
Excitotoxicity plays a key role during insults to the developing brain such as neonatal encephalopathy, stroke, and encephalopathy of prematurity. Such insults affect many thousands of infants each year. Excitotoxicity causes frank lesions due to cell death and gliosis and disturbs normal developmental process, leading to deficits in learning, memory, and social integration that persist into adulthood. Understanding the underlying processes of the acute effects of excitotoxicity and its persistence during brain maturation provides an opportunity to identify mechanistic or diagnostic biomarkers, thus enabling and designing possible therapies...
May 12, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28490444/inhibiting-glucosylceramide-synthase-exacerbates-cisplatin-induced-acute-kidney-injury
#17
Tess V Dupre, Mark A Doll, Parag P Shah, Cierra N Sharp, Deanna Siow, Judit Megyesi, James Shayman, Alicja Bielwska, Jacek Bielawski, Levi J Beverly, Maria Hernandez-Corbacho, Christopher J Clarke, Ashley J Snider, Rick G Schnellmann, Lina M Obeid, Yusuf A Hannun, Leah J Siskind
Acute kidney injury (AKI), resulting from chemotherapeutic agents such as cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI involves apoptotic and necrotic cell death, pathways regulated by sphingolipids such as ceramide and glucosylceramide. Results from this study indicate that C57BL/6J mice treated with cisplatin had increased ceramide and hexosylceramide levels in the renal cortex 72 h following cisplatin treatment. Pre-treatment of mice with inhibitors of acid sphingomyelinase and de novo ceramide synthesis (amitriptyline and myriocin, respectively) prevented accumulation of ceramides and hexosylceramide in the renal cortex and protected from cisplatin-induced AKI...
May 10, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28486997/the-antifungal-aureobasidin-a-and-an-analogue-are-active-against-the-protozoan-parasite-toxoplasma-gondii-but-do-not-inhibit-sphingolipid-biosynthesis
#18
A Q I Alqaisi, A J Mbekeani, M Bassas Llorens, A P Elhammer, P W Denny
Toxoplasma gondii is an obligate intracellular protozoan parasite of the phylum Apicomplexa, and toxoplasmosis is an important disease of both humans and economically important animals. With a limited array of drugs available there is a need to identify new therapeutic compounds. Aureobasidin A (AbA) is an antifungal that targets the essential inositol phosphorylceramide (IPC, sphingolipid) synthase in pathogenic fungi. This natural cyclic depsipeptide also inhibits Toxoplasma proliforation, with the protozoan IPC synthase orthologue proposed as the target...
May 10, 2017: Parasitology
https://www.readbyqxmd.com/read/28486481/temporal-changes-in-sphingolipids-and-systemic-insulin-sensitivity-during-the-transition-from-gestation-to-lactation
#19
J Eduardo Rico, Sina Saed Samii, Alice T Mathews, Jacqueline Lovett, Norman J Haughey, Joseph W McFadden
Reduced insulin action develops naturally during the peripartum to ensure maternal nutrient delivery to the fetus and neonate. However, increased insulin resistance can facilitate excessive lipolysis which in turn promotes metabolic disease in overweight dairy cattle. Increased fatty acid availability favors the accumulation of the sphingolipid ceramide and is implicated in the pathogenesis of insulin resistance, however, the relationship between sphingolipid metabolism and insulin resistance during the peripartum remains largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28484432/rice-bran-and-probiotics-alter-the-porcine-large-intestine-and-serum-metabolomes-for-protection-against-human-rotavirus-diarrhea
#20
Nora Jean Nealon, Lijuan Yuan, Xingdong Yang, Elizabeth P Ryan
Human rotavirus (HRV) is a leading cause of severe childhood diarrhea, and there is limited vaccine efficacy in the developing world. Neonatal gnotobiotic pigs consuming a prophylactic synbiotic combination of probiotics and rice bran (Pro+RB) did not exhibit HRV diarrhea after challenge. Multiple immune, gut barrier protective, and anti-diarrheal mechanisms contributed to the prophylactic efficacy of Pro+RB when compared to probiotics (Pro) alone. In order to understand the molecular signature associated with diarrheal protection by Pro+RB, a global non-targeted metabolomics approach was applied to investigate the large intestinal contents and serum of neonatal gnotobiotic pigs...
2017: Frontiers in Microbiology
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