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Ceramide platforms

Miguel A Martín-Acebes, Ángela Vázquez-Calvo, Juan-Carlos Saiz
Flaviviruses are emerging arthropod-borne pathogens that cause life-threatening diseases such as yellow fever, dengue, West Nile encephalitis, tick-borne encephalitis, Kyasanur Forest disease, tick-borne encephalitis, or Zika disease. This viral genus groups >50 viral species of small enveloped plus strand RNA virus that are phylogenetically closely related to hepatitis C virus. Importantly, the flavivirus life cycle is intimately associated to host cell lipids. Along this line, flaviviruses rearrange intracellular membranes from the endoplasmic-reticulum of the infected cells to develop adequate platforms for viral replication and particle biogenesis...
October 1, 2016: Progress in Lipid Research
Jace W Jones, Claire L Carter, Fei Li, Jianshi Yu, Keely Pierzchalski, Isabel L Jackson, Zeljko Vujaskovic, Maureen A Kane
Lipids represent biologically ubiquitous and highly dynamic molecules in terms of abundance and structural diversity. Whereas the potential for lipids to inform on disease/injury is promising, their unique characteristics make detection and identification of lipids from biological samples analytically demanding. We report the use of ultraperformance convergence chromatography (UPC(2) ), a variant of supercritical fluid chromatography, coupled to high resolution, data-independent tandem mass spectrometry for characterization of total lipid extracts from mouse lung tissue...
August 24, 2016: Biomedical Chromatography: BMC
Alexei Gorelik, Katalin Illes, Leonhard X Heinz, Giulio Superti-Furga, Bhushan Nagar
Acid sphingomyelinase (ASMase, ASM, SMPD1) converts sphingomyelin into ceramide, modulating membrane properties and signal transduction. Inactivating mutations in ASMase cause Niemann-Pick disease, and its inhibition is also beneficial in models of depression and cancer. To gain a better understanding of this critical therapeutic target, we determined crystal structures of mammalian ASMase in various conformations. The catalytic domain adopts a calcineurin-like fold with two zinc ions and a hydrophobic track leading to the active site...
2016: Nature Communications
Zhexue Wu, Jong Cheol Shon, Doohyun Lee, Kab-Tae Park, Chang Seo Park, Taeho Lee, Hye Suk Lee, Kwang-Hyeon Liu
Skin ceramides are sphingolipids consisting of sphingoid bases, which are linked to fatty acids via an amide bond. Typical fatty acid acyl chains are composed of α-hydroxy fatty acid (A), esterified ω-hydroxy fatty acid (EO), non-hydroxy fatty acid (N), and ω-hydroxy fatty acid (O). We recently established a lipidomic platform to identify skin ceramides with non-hydroxyacyl chains using tandem mass spectrometry. We expanded our study to establish a lipidomic platform to identify skin ceramides with α-hydroxyacyl chains...
March 2016: Analytical and Bioanalytical Chemistry
Fang Bian, Bin Xiong, Xiaoyan Yang, Si Jin
Transcytosis, a widely described process concerning transport of macromolecules between the apical and basolateral sides in various cell types, is extremely important for multicellular organisms to selectively exchange materials in different microenvironments while maintaining cellular and body homeostasis. Uncontrolled transcytosis is involved in a wide range of pathophysiological processes. Lipid rafts (LRs), the sphingolipid and cholesterol-enriched membrane microdomains, enable to form different functional membrane macrodomains or platforms upon stimulations...
2016: Frontiers in Bioscience (Landmark Edition)
Shravan Kumar Sriraman, Jiayi Pan, Can Sarisozen, Ed Luther, Vladimir Torchilin
Current research in cancer therapy is beginning to shift toward the use of combinational drug treatment regimens. However, the efficient delivery of drug combinations is governed by a number of complex factors in the clinical setting. Therefore, the ability to synchronize the pharmacokinetics of the individual therapeutic agents present in combination not only to allow for simultaneous tumor accumulation but also to allow for a synergistic relationship at the intracellular level could prove to be advantageous...
February 1, 2016: Molecular Pharmaceutics
Tingting Zhang, Si Chen, Xinle Liang, Hong Zhang
This article describes the development of a lipidomic platform consisting of a 4000 QTRAP mass spectrometer and a self-installed sample inlet system to indentify and quantify 12 phospholipid and five sphingolipid classes from lipid-rich brain tissues of mouse, duck, and salmon. The total mass spectrometry analysis time per sample was 30 min, including 14 min for direct infusion for phospholipids and sulfatide in precursor ion scanning mode or neutral loss scanning mode, and 16 min for liquid-chromatographic separation of ceramide, sphingomyelin, monohexosylceramide, and dihexosylceramide in multiple reaction monitoring mode...
August 2015: Analytical and Bioanalytical Chemistry
Mariana Figuera-Losada, Marigo Stathis, Joelle M Dorskind, Ajit G Thomas, Veera Venkata Ratnam Bandaru, Seung-Wan Yoo, Nicholas J Westwood, Graeme W Rogers, Justin C McArthur, Norman J Haughey, Barbara S Slusher, Camilo Rojas
Ceramide is a bioactive lipid that plays an important role in stress responses leading to apoptosis, cell growth arrest and differentiation. Ceramide production is due in part to sphingomyelin hydrolysis by sphingomyelinases. In brain, neutral sphingomyelinase 2 (nSMase2) is expressed in neurons and increases in its activity and expression have been associated with pro-inflammatory conditions observed in Alzheimer's disease, multiple sclerosis and human immunodeficiency virus (HIV-1) patients. Increased nSMase2 activity translates into higher ceramide levels and neuronal cell death, which can be prevented by chemical or genetic inhibition of nSMase2 activity or expression...
2015: PloS One
Hervé Agaisse, Isabelle Derré
Productive developmental cycle of the obligate intracellular bacterial pathogen Chlamydia trachomatis depends on the interaction of the replicative vacuole, named the inclusion, with cellular organelles. We have recently reported the formation of ER-Inclusion membrane contact sites (MCSs), where the endoplasmic reticulum (ER) is in apposition to the inclusion membrane. These platforms contain the C. trachomatis inclusion membrane protein IncD, the mammalian ceramide transfer protein CERT and the ER resident proteins VAPA/B and were proposed to play a role in the non-vesicular trafficking of lipids to the inclusion...
2015: PloS One
Hanna M G Barriga, Edward S Parsons, Nicola L C McCarthy, Oscar Ces, John M Seddon, Robert V Law, Nicholas J Brooks
Ceramides are a group of sphingolipids that act as highly important signaling molecules in a variety of cellular processes including differentiation and apoptosis. The predominant in vivo synthetic pathway for ceramide formation is via sphingomyelinase catalyzed hydrolysis of sphingomyelin. The biochemistry of this essential pathway has been studied in detail; however, there is currently a lack of information on the structural behavior of sphingomyelin- and ceramide-rich model membrane systems, which is essential for developing a bottom-up understanding of ceramide signaling and platform formation...
March 31, 2015: Langmuir: the ACS Journal of Surfaces and Colloids
Žofie Sovová, Karel Berka, Michal Otyepka, Petr Jurečka
Ceramides are lipids that are involved in numerous biologically important structures (e.g., the stratum corneum and ceramide-rich platforms) and processes (e.g., signal transduction and membrane fusion), but their behavior is not fully understood. We report coarse-grain force field parameters for N-lignocerylsphingosine (ceramide NS, also known as ceramide 2) that are consistent with the Martini force field. These parameters were optimized for simulations in the gel phase and validated against atomistic simulations...
March 12, 2015: Journal of Physical Chemistry. B
Carmen Garcia-Ruiz, Albert Morales, José C Fernández-Checa
Glycosphingolipids (GSLs) are a family of bioactive lipids that in addition to their role in the regulation of structural properties of membrane bilayers have emerged as crucial players in many biological processes and signal transduction pathways. Rather than being uniformly distributed within membrane bilayers, GSLs are localized in selective domains called lipid rafts where many signaling platforms operate. One of the most important functions of GSLs, particularly ceramide, is their ability to regulate cell death pathways and hence cell fate...
May 2015: Apoptosis: An International Journal on Programmed Cell Death
Jürgen Schneider-Schaulies, Sibylle Schneider-Schaulies
Viruses exploit membranes and their components such as sphingolipids in all steps of their life cycle including attachment and membrane fusion, intracellular transport, replication, protein sorting and budding. Examples for sphingolipid-dependent virus entry are found for: human immunodeficiency virus (HIV), which besides its protein receptors also interacts with glycosphingolipids (GSLs); rhinovirus, which promotes the formation of ceramide-enriched platforms and endocytosis; or measles virus (MV), which induces the surface expression of its own receptor CD150 via activation of sphingomyelinases (SMases)...
June 2015: Biological Chemistry
Nuno A Fonseca, Lígia C Gomes-da-Silva, Vera Moura, Sérgio Simões, João Nuno Moreira
Drug resistance remains the Achilles tendon undermining the success of chemotherapy. It has been recognized that success requires the identification of compounds that, when combined, lead to synergistic tumor inhibition while simultaneously minimizing systemic toxicity. However, in vivo application of such protocols is dependent on the ability to deliver the appropriate drug ratio at the tumor level. In this respect, nanotechnology-based delivery platforms, like liposomes, offer an elegant solution for the in vivo translation of such strategy...
December 28, 2014: Journal of Controlled Release: Official Journal of the Controlled Release Society
Nadine Beckmann, Deepa Sharma, Erich Gulbins, Katrin Anne Becker, Bärbel Edelmann
Amitriptyline, a tricyclic antidepressant, has been used in the clinic to treat a number of disorders, in particular major depression and neuropathic pain. In the 1970s the ability of tricyclic antidepressants to inhibit acid sphingomyelinase (ASM) was discovered. The enzyme ASM catalyzes the hydrolysis of sphingomyelin to ceramide. ASM and ceramide were shown to play a crucial role in a wide range of diseases, including cancer, cystic fibrosis, diabetes, Alzheimer's disease, and major depression, as well as viral (e...
2014: Frontiers in Physiology
Chérine Bechara, Manjula Pallerla, Fabienne Burlina, Françoise Illien, Sophie Cribier, Sandrine Sagan
Among non-invasive cell delivery strategies, cell-penetrating peptide (CPP) vectors represent interesting new tools. To get fundamental knowledge about the still debated internalisation mechanisms of these peptides, we modified the membrane content of cells, typically by hydrolysis of sphingomyelin or depletion of cholesterol from the membrane outer leaflet. We quantified and visualised the effect of these viable cell surface treatments on the internalisation efficiency of different CPPs, among which the most studied Tat, R9, penetratin and analogues, that all carry the N-terminal biotin-Gly4 tag cargo...
February 2015: Cellular and Molecular Life Sciences: CMLS
Sonali Kapse-Mistry, Thirumala Govender, Rohit Srivastava, Mayur Yergeri
Different mechanisms in cancer cells become resistant to one or more chemotherapeutics is known as multidrug resistance (MDR) which hinders chemotherapy efficacy. Potential factors for MDR includes enhanced drug detoxification, decreased drug uptake, increased intracellular nucleophiles levels, enhanced repair of drug induced DNA damage, overexpression of drug transporter such as P-glycoprotein(P-gp), multidrug resistance-associated proteins (MRP1, MRP2), and breast cancer resistance protein (BCRP). Currently nanoassemblies such as polymeric/solid lipid/inorganic/metal nanoparticles, quantum dots, dendrimers, liposomes, micelles has emerged as an innovative, effective, and promising platforms for treatment of drug resistant cancer cells...
2014: Frontiers in Pharmacology
Alexander Simonis, Sabrina Hebling, Erich Gulbins, Sibylle Schneider-Schaulies, Alexandra Schubert-Unkmeir
The interaction with brain endothelial cells is central to the pathogenicity of Neisseria meningitidis infections. Here, we show that N. meningitidis causes transient activation of acid sphingomyelinase (ASM) followed by ceramide release in brain endothelial cells. In response to N. meningitidis infection, ASM and ceramide are displayed at the outer leaflet of the cell membrane and condense into large membrane platforms which also concentrate the ErbB2 receptor. The outer membrane protein Opc and phosphatidylcholine-specific phospholipase C that is activated upon binding of the pathogen to heparan sulfate proteoglycans, are required for N...
June 2014: PLoS Pathogens
Jon V Busto, Aritz B García-Arribas, Jesús Sot, Alejandro Torrecillas, Juan C Gómez-Fernández, Félix M Goñi, Alicia Alonso
Lipid lateral segregation into specific domains in cellular membranes is associated with cell signaling and metabolic regulation. This phenomenon partially arises as a consequence of the very distinct bilayer-associated lipid physico-chemical properties that give rise to defined phase states at a given temperature. Until now lamellar gel (Lβ) phases have been described in detail in single or two-lipid systems. Using x-ray scattering, differential scanning calorimetry, confocal fluorescence microscopy, and atomic force microscopy, we have characterized phases of ternary lipid compositions in the presence of saturated phospholipids, cholesterol, and palmitoyl ceramide mixtures...
February 4, 2014: Biophysical Journal
Jung-Hoon Shin, Jong Cheol Shon, Kyohoon Lee, Sunki Kim, Chang Seo Park, Eung Ho Choi, Choong Hwan Lee, Hye Suk Lee, Kwang-Hyeon Liu
The stratum corneum (SC) is the outermost layer of skin that functions as a barrier and protects against environmental influences and transepidermal water loss. Its unique morphology consists of keratin-enriched corneocytes embedded in a distinctive mixture of lipids containing mainly ceramides, free fatty acids, and cholesterol. Ceramides are sphingolipids consisting of sphingoid bases, which are linked to fatty acids by an amide bond. Typical sphingoid bases in the skin are composed of dihydrosphingosine (dS), sphingosine (S), phytosphingosine (P), and 6-hydroxysphingosine (H), and the fatty acid acyl chains are composed of non-hydroxy fatty acid (N), α-hydroxy fatty acid (A), ω-hydroxy fatty acid (O), and esterified ω-hydroxy fatty acid (E)...
March 2014: Analytical and Bioanalytical Chemistry
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