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https://www.readbyqxmd.com/read/27913291/a-saposin-deficiency-model-in-drosophila-lysosomal-storage-progressive-neurodegeneration-and-sensory-physiological-decline
#1
Samantha J Hindle, Sarita Hebbar, Dominik Schwudke, Christopher J Elliott, Sean T Sweeney
Saposin deficiency is a childhood neurodegenerative lysosomal storage disorder (LSD) that can cause premature death within three months of life. Saposins are activator proteins that promote the function of lysosomal hydrolases that mediate the degradation of sphingolipids. There are four saposin proteins in humans, which are encoded by the prosaposin gene. Mutations causing an absence or impaired function of individual saposins or the whole prosaposin gene lead to distinct LSDs due to the storage of different classes of sphingolipids...
November 29, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27910928/high-throughput-chinmedomics-based-prediction-of-effective-components-and-targets-from-herbal-medicine-as1350
#2
Qi Liu, Aihua Zhang, Liang Wang, Guangli Yan, Hongwei Zhao, Hui Sun, Shiyu Zou, Jinwei Han, Chung Wah Ma, Ling Kong, Xiaohang Zhou, Yang Nan, Xijun Wang
This work was designed to explore the effective components and targets of herbal medicine AS1350 and its effect on "Kidney-Yang Deficiency Syndrome" (KYDS) based on a chinmedomics strategy which is capable of directly discovering and predicting the effective components, and potential targets, of herbal medicine. Serum samples were analysed by UPLC-MS combined with pattern recognition analysis to identify the biomarkers related to the therapeutic effects. Interestingly, the effectiveness of AS1350 against KYDS was proved by the chinmedomics method and regulated the biomarkers and targeting of metabolic disorders...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909176/editorial-feeling-the-burn-sphingolipids-and-infection-risk-after-thermal-injury
#3
EDITORIAL
Julia K Bohannon, Edward R Sherwood
No abstract text is available yet for this article.
December 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27907090/forkhead-box-c1-regulates-human-primary-keratinocyte-terminal-differentiation
#4
Lianghua Bin, Liehua Deng, Hengwen Yang, Leqing Zhu, Xiao Wang, Michael G Edwards, Brittany Richers, Donald Y M Leung
The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC) terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq) profiling approach, we found that forkhead box c 1 (FOXC1) was significantly up-regulated in human normal primary KC during the course of differentiation...
2016: PloS One
https://www.readbyqxmd.com/read/27901468/loss-of-frataxin-activates-the-iron-sphingolipid-pdk1-mef2-pathway-in-mammals
#5
Kuchuan Chen, Tammy Szu-Yu Ho, Guang Lin, Kai Li Tan, Matthew N Rasband, Hugo J Bellen
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by mutations in Frataxin (FXN). Loss of FXN causes impaired mitochondrial function and iron homeostasis. An elevated production of reactive oxygen species (ROS) was previously proposed to contribute to the pathogenesis of FRDA. We recently showed that loss of frataxin homolog (fh), a Drosophila homolog of FXN, causes a ROS independent neurodegeneration in flies (Chen et al., 2016). In fh mutants, iron accumulation in the nervous system enhances the synthesis of sphingolipids, which in turn activates 3-phosphoinositide dependent protein kinase-1 (Pdk1) and myocyte enhancer factor-2 (Mef2) to trigger neurodegeneration of adult photoreceptors...
November 30, 2016: ELife
https://www.readbyqxmd.com/read/27896622/caveolin-proteins-a-molecular-insight-into-disease
#6
REVIEW
Hongli Yin, Tianyi Liu, Ying Zhang, Baofeng Yang
Caveolae are a kind of specific cystic structures of lipid rafts in the cytoplasmic membrane and are rich in cholesterol and sphingolipids. In recent years, many researchers have found that both caveolins and caveolae play a role in the development of various human diseases, including coronary heart disease, hypertension, and nervous system disorders. The specific mechanisms by which caveolins induce diseases have been a topic of interest. However, a number of detailed molecular mechanisms remain poorly understood...
November 28, 2016: Frontiers of Medicine
https://www.readbyqxmd.com/read/27895225/loss-of-inositol-phosphorylceramide-sphingolipid-mannosylation-induces-plant-immune-responses-and-reduces-cellulose-content-in-arabidopsis
#7
Lin Fang, Toshiki Ishikawa, Emilie A Rennie, Gosia M Murawska, Jeemeng Lao, Jingwei Yan, Alex Yl Tsai, Edward E K Baidoo, Jun Xu, Jay D Keasling, Taku Demura, Maki Kawai-Yamada, Henrik Vibe Scheller, Jenny C Mortimer
Glycosylinositol phosphorylceramides (GIPCs) are a class of glycosylated sphingolipids found in plants, fungi, and protozoa. These lipids are abundant in the plant plasma membrane, forming ~25% of total plasma membrane lipids. Little is known about the function of the glycosylated headgroup, but two recent studies have indicated that they play a key role in plant signaling and defense. Here, we show that a member of glycosyltransferase (GT) family 64, previously named ECTOPICALLY PARTING CELLS1 (EPC1), is likely a Golgi-localized GIPC-specific mannosyl-transferase, which we renamed GIPC MANNOSYL-TRANSFERASE1 (GMT1)...
November 28, 2016: Plant Cell
https://www.readbyqxmd.com/read/27888692/mitochondrial-gsh-replenishment-as-a-potential-therapeutic-approach-for-niemann-pick-type-c-disease
#8
Sandra Torres, Nuria Matías, Anna Baulies, Susana Nuñez, Cristina Alarcon-Vila, Laura Martinez, Natalia Nuño, Anna Fernandez, Joan Caballeria, Thierry Levade, Alba Gonzalez-Franquesa, Pablo Garcia-Rovés, Elisa Balboa, Silvana Zanlungo, Gemma Fabrías, Josefina Casas, Carlos Enrich, Carmen Garcia-Ruiz, José C Fernández-Checa
Niemann Pick type C (NPC) disease is a progressive lysosomal storage disorder caused by mutations in genes encoding NPC1/NPC2 proteins, characterized by neurological defects, hepatosplenomegaly and premature death. While the primary biochemical feature of NPC disease is the intracellular accumulation of cholesterol and gangliosides, predominantly in endolysosomes, mitochondrial cholesterol accumulation has also been reported. As accumulation of cholesterol in mitochondria is known to impair the transport of GSH into mitochondria, resulting in mitochondrial GSH (mGSH) depletion, we investigated the impact of mGSH recovery in NPC disease...
November 20, 2016: Redox Biology
https://www.readbyqxmd.com/read/27883090/sphingosine-1-phosphate-lyase-ablation-disrupts-presynaptic-architecture-and-function-via-an-ubiquitin-proteasome-mediated-mechanism
#9
Daniel N Mitroi, André U Deutschmann, Maren Raucamp, Indulekha Karunakaran, Konstantine Glebov, Michael Hans, Jochen Walter, Julie Saba, Markus Gräler, Dan Ehninger, Elena Sopova, Oleg Shupliakov, Dieter Swandulla, Gerhild van Echten-Deckert
The bioactive lipid sphingosine 1-phosphate (S1P) is a degradation product of sphingolipids that are particularly abundant in neurons. We have shown previously that neuronal S1P accumulation is toxic leading to ER-stress and an increase in intracellular calcium. To clarify the neuronal function of S1P, we generated brain-specific knockout mouse models in which S1P-lyase (SPL), the enzyme responsible for irreversible S1P cleavage was inactivated. Constitutive ablation of SPL in the brain (SPL(fl/fl/Nes)) but not postnatal neuronal forebrain-restricted SPL deletion (SPL(fl/fl/CaMK)) caused marked accumulation of S1P...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881717/localization-of-1-deoxysphingolipids-to-mitochondria-induces-mitochondrial-dysfunction
#10
Irina Alecu, Andrea Tedeschi, Natascha Behler, Klaus Wunderling, Christian Lamberz, Mario A R Lauterbach, Anne Gaebler, Daniela Ernst, Paul P Van Veldhoven, Ashraf Al-Amoudi, Eicke Latz, Alaa Othman, Lars Kuerschner, Thorsten Hornemann, Frank Bradke, Christoph Thiele, Anke Penno
1-Deoxysphingolipids (deoxySLs) are atypical sphingolipids that are elevated in the plasma of patients with type 2 diabetes and hereditary sensory and autonomic neuropathy type 1 (HSAN1). Clinically, diabetic neuropathy and HSAN1 are very similar, suggesting the involvement of deoxySLs in the pathology of both diseases. However, very little is known about the biology of these lipids and the underlying pathomechanism. We synthesized an alkyne analogue of 1-deoxysphinganine (doxSA), the metabolic precursor of all deoxySLs, to trace the metabolism and localization of deoxySLs...
November 23, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27881660/the-norovirus-ns3-protein-is-a-dynamic-lipid-and-microtubule-associated-protein-involved-in-viral-rna-replication
#11
Ben Cotton, Jennifer L Hyde, Soroush T Sarvestani, Stanislav V Sosnovtsev, Kim Y Green, Peter A White, Jason M Mackenzie
: Norovirus (NoV) infections are a significant health burden to society yet the lack of reliable tissue culture systems has hampered the development of appropriate antiviral therapies. Here we show that the NoV NS3 protein, derived from murine NoV (MNV), is intimately associated with the MNV replication complex and the viral replication intermediate dsRNA. We have observed that when expressed individually MNV NS3 and NS3 encoded by human Norwalk virus (NV) induced the formation of distinct vesicle-like structures that did not co-localise with any particular protein markers to cellular organelles, but localised to cellular membranes, in particular those high in cholesterol content...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27881065/lipids-at-the-cross-road-of-autoimmunity-in-multiple-sclerosis
#12
Marcella Reale, Silvia Sánchez-Ramón
Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by demyelination and neurodegeneration, driven by a Th17/Th1-immune response, which afflicts mainly young women. Although MS causes are not completely known, it is notorious that the disease is characterized by an extended focal degradation of the myelin sheath, with ulterior axon and neuronal damage. Lipid molecules play a main dual role in MS, both as target molecules of myelin destruction and as mediators of inflammation...
November 22, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27877101/from-molecules-to-the-clinic-linking-schizophrenia-and-metabolic-syndrome-through-sphingolipids-metabolism
#13
REVIEW
Rolando I Castillo, Leonel E Rojo, Marcela Henriquez-Henriquez, Hernán Silva, Alejandro Maturana, María J Villar, Manuel Fuentes, Pablo A Gaspar
Metabolic syndrome (MS) is a prevalent and severe comorbidity observed in schizophrenia (SZ). The exact nature of this association is controversial and very often accredited to the effects of psychotropic medications and disease-induced life-style modifications, such as inactive lifestyle, poor dietary choices, and smoking. However, drug therapy and disease-induced lifestyle factors are likely not the only factors contributing to the observed converging nature of these conditions, since an increased prevalence of MS is also observed in first episode and drug-naïve psychosis populations...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27875779/novel-pyrimidine-2-4-dione-1-2-3-triazole-and-furo-2-3-d-pyrimidine-2-one-1-2-3-triazole-hybrids-as-potential-anti-cancer-agents-synthesis-computational-and-x-ray-analysis-and-biological-evaluation
#14
Tomislav Gregorić, Mirela Sedić, Petra Grbčić, Andrea Tomljenović Paravić, Sandra Kraljević Pavelić, Mario Cetina, Robert Vianello, Silvana Raić-Malić
Regioselective 1,4-disubstituted 1,2,3-triazole tethered pyrimidine-2,4-dione derivatives (5-23) were successfully prepared by the copper(I)-catalyzed click chemistry. While known palladium/copper-cocatalyzed method based on Sonogashira cross-coupling followed by the intramolecular 5-endo-dig ring closure generated novel 6-alkylfuro[2,3-d]pyrimidine-2-one-1,2,3-triazole hybrids (24b-37b), a small library of their 5-alkylethynyl analogs (24a-37a) was synthesized and described for the first time by tandem terminal alkyne dimerization and subsequent 5-endo-trig cyclization, which was additionally corroborated with computational and X-ray crystal structure analyses...
November 14, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27872310/efficient-replacement-of-plasma-membrane-outer-leaflet-phospholipids-and-sphingolipids-in-cells-with-exogenous-lipids
#15
Guangtao Li, JiHyun Kim, Zhen Huang, Johnna R St Clair, Deborah A Brown, Erwin London
Our understanding of membranes and membrane lipid function has lagged far behind that of nucleic acids and proteins, largely because it is difficult to manipulate cellular membrane lipid composition. To help solve this problem, we show that methyl-α-cyclodextrin (MαCD)-catalyzed lipid exchange can be used to maximally replace the sphingolipids and phospholipids in the outer leaflet of the plasma membrane of living mammalian cells with exogenous lipids, including unnatural lipids. In addition, lipid exchange experiments revealed that 70-80% of cell sphingomyelin resided in the plasma membrane outer leaflet; the asymmetry of metabolically active cells was similar to that previously defined for erythrocytes, as judged by outer leaflet lipid composition; and plasma membrane outer leaflet phosphatidylcholine had a significantly lower level of unsaturation than phosphatidylcholine in the remainder of the cell...
November 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27872144/cytotoxic-1-deoxysphingolipids-are-metabolized-by-a-cytochrome-p450-dependent-pathway
#16
Irina Alecu, Alaa Othman, Anke Penno, Essa M Saied, Christoph Arenz, Arnold von Eckardstein, Thorsten Hornemann
1-Deoxysphingolipids (1-deoxySLs) are atypical sphingolipids which are formed when serine palmitoyltransferase condenses palmitoyl-CoA with alanine instead of serine during sphingolipid synthesis. 1-DeoxySLs are toxic to neurons and pancreatic beta-cells. Pathologically elevated 1-deoxySLs cause the inherited neuropathy HSAN1 and are also found in type 2 diabetes. Diabetic sensory polyneuropathy and HSAN1 are clinically very similar, suggesting that 1-deoxySLs may be implicated in both pathologies. 1-DeoxySLs are considered to be dead-end metabolites, as they lack the C1-hydroxyl group which is essential for the canonical degradation of sphingolipids...
November 21, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27870891/oxldl-and-eldl-induced-membrane-microdomains-in-human-macrophages
#17
Stefan Wallner, Margot Grandl, Gerhard Liebisch, Markus Peer, Evelyn Orsó, Alexander Sigrüner, Andrzej Sobota, Gerd Schmitz
BACKGROUND: Extravasation of macrophages and formation of lipid-laden foam cells are key events in the development and progression of atherosclerosis. The degradation of atherogenic lipoproteins subsequently leads to alterations in cellular lipid metabolism that influence inflammatory signaling. Especially sphingolipids and ceramides are known to be involved in these processes. We therefore analyzed monocyte derived macrophages during differentiation and after loading with enzymatically (eLDL) and oxidatively (oxLDL) modified low-density lipoproteins (LDL)...
2016: PloS One
https://www.readbyqxmd.com/read/27869314/runx1-orchestrates-sphingolipid-metabolism-and-glucocorticoid-resistance-in-lymphomagenesis
#18
A Kilbey, A Terry, S Wotton, G Borland, Q Zhang, N Mackay, A McDonald, M Bell, M J O Wakelam, E R Cameron, J C Neil
The three-membered RUNX gene family includes RUNX1, a major mutational target in human leukemias, and displays hallmarks of both tumour suppressors and oncogenes. In mouse models the Runx genes appear to act as conditional oncogenes, as ectopic expression is growth suppressive in normal cells but drives lymphoma development potently when combined with over-expressed Myc or loss of p53. Clues to underlying mechanisms emerged previously from murine fibroblasts where ectopic expression of any of the Runx genes promotes survival through direct and indirect regulation of key enzymes in sphingolipid metabolism associated with a shift in the 'sphingolipid rheostat' from ceramide to sphingosine-1-phosphate (S1P)...
November 21, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27866974/sphingolipids-in-neutrophil-function-and-inflammatory-responses-mechanisms-and-implications-for-intestinal-immunity-and-inflammation-in-ulcerative-colitis
#19
REVIEW
Mel Pilar Espaillat, Richard R Kew, Lina M Obeid
Bioactive sphingolipids are regulators of immune cell function and play critical roles in inflammatory conditions including ulcerative colitis. As one of the major forms of inflammatory bowel disease, ulcerative colitis pathophysiology is characterized by an aberrant intestinal inflammatory response that persists causing chronic inflammation and tissue injury. Innate immune cells play an integral role in normal intestinal homeostasis but their dysregulation is thought to contribute to the pathogenesis of ulcerative colitis...
November 14, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27857690/interferon-beta-increases-plasma-ceramides-of-specific-chain-length-in-multiple-sclerosis-patients-unlike-fingolimod-or-natalizumab
#20
Florian M Ottenlinger, Christoph A Mayer, Nerea Ferreirós, Yannick Schreiber, Anja Schwiebs, Katrin G Schmidt, Hanns Ackermann, Josef M Pfeilschifter, Heinfried H Radeke
Fingolimod is used for the treatment of multiple sclerosis (MS) and targets receptors for the bioactive sphingolipid sphingosine-1-phosphate (S1P). Whether fingolimod or other MS therapies conversely affect plasma concentrations of sphingolipids has, however, not yet been analyzed. Herein, we quantified 15 representative sphingolipid species by mass spectrometry in plasma from relapsing-remitting MS patients currently under fingolimod (n = 24), natalizumab (n = 16), or IFN-β (n = 18) treatment. Healthy controls (n = 21) and untreated MS patients (n = 11) served as control groups...
2016: Frontiers in Pharmacology
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