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https://www.readbyqxmd.com/read/28230380/effects-of-6-hydroxyceramides-on-the-thermotropic-phase-behavior-and-permeability-of-model-skin-lipid-membranes
#1
Andrej Kovacik, Michaela Silarova, Petra Pullmannová, Jaroslav Maixner, Katerina Vavrova
Ceramides (Cer) based on 6-hydroxysphingosine are important components of the human skin barrier, the stratum corneum. Although diminished concentrations of 6-hydroxyCer have been detected in skin diseases such as atopic dermatitis, our knowledge of these unusual sphingolipids, which have only been found in the skin, is limited. In this work, we investigate the biophysical behavior of N-lignoceroyl 6-hydroxysphingosine (Cer NH) in multilamellar lipid membranes composed of Cer/free fatty acids (C16-C24)/cholesterol/cholesteryl sulfate...
February 23, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28225753/complement-drives-glucosylceramide-accumulation-and-tissue-inflammation-in-gaucher-disease
#2
Manoj K Pandey, Thomas A Burrow, Reena Rani, Lisa J Martin, David Witte, Kenneth D Setchell, Mary A Mckay, Albert F Magnusen, Wujuan Zhang, Benjamin Liou, Jörg Köhl, Gregory A Grabowski
Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Here we show that activation of complement C5a and C5a receptor 1 (C5aR1) controls GC accumulation and the inflammatory response in experimental and clinical Gaucher disease...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28225091/phase-separation-in-ceramide-np-containing-lipid-model-membranes-neutron-diffraction-and-solid-state-nmr
#3
Annett Schroeter, Sören Stahlberg, Barbora Školová, Stefan Sonnenberger, Adina Eichner, Daniel Huster, Kateřina Vávrová, Thomas Hauß, Bodo Dobner, Reinhard H H Neubert, Alexander Vogel
The stratum corneum is the outermost layer of the skin and protects the organism against external influences as well as water loss. It consists of corneocytes embedded in a mixture of ceramides, fatty acids, and cholesterol in a molar ratio of roughly 1 : 1 : 1. The unique structural and compositional arrangement of these stratum corneum lipids is responsible for the skin barrier properties. Many studies investigated the organization of these barrier lipids and, in particular, the exact conformation of ceramides...
February 22, 2017: Soft Matter
https://www.readbyqxmd.com/read/28223543/role-of-caspases-in-cd95-induced-biphasic-activation-of-acid-sphingomyelinase
#4
Mario Stephan, Bärbel Edelmann, Supandi Winoto-Morbach, Ottmar Janssen, Uwe Bertsch, Cristiana Perrotta, Stefan Schütze, Jürgen Fritsch
Acid sphingomyelinase (A-SMase) plays an important role in the initiation of CD95 signaling by forming ceramide-enriched membrane domains that enable clustering and activation of the death receptors. In TNF-R1 and TRAIL-R1/R2 signaling, A-SMase also contributes to the lysosomal apoptosis pathway triggered by receptor internalization. Here, we investigated the molecular mechanism of CD95-mediated A-SMase activation, demonstrating that A-SMase is located in internalized CD95-receptosomes and is activated by the CD95/CD95L complex in a biphasic manner...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223344/an-intestinal-farnesoid-x-receptor-ceramide-signaling-axis-modulates-hepatic-gluconeogenesis-in-mice
#5
Cen Xie, Changtao Jiang, Jingmin Shi, Xiaoxia Gao, Dongxue Sun, Lulu Sun, Ting Wang, Shogo Takahashi, Mallappa Anitha, Kristopher W Krausz, Andrew D Patterson, Frank J Gonzalez
Increasing evidence supports the view that intestinal farnesoid X receptor (FXR) is involved in glucose tolerance and that FXR signaling can be profoundly impacted by the gut microbiota. Selective manipulation of the gut microbiota-FXR signaling axis was reported to significantly impact glucose intolerance, but the precise molecular mechanism remains largely unknown. Here, caffeic acid phenethyl ester (CAPE), an over-the-counter dietary supplement and an inhibitor of bacterial bile salt hydrolase, increased levels of intestinal tauro-β-muricholic acid, which selectively suppresses intestinal FXR signaling...
March 2017: Diabetes
https://www.readbyqxmd.com/read/28222420/camalexin-induced-cell-membrane-scrambling-and-cell-shrinkage-in-human-erythrocytes
#6
Mustafa Almasry, Mohamed Jemaà, Morena Mischitelli, Florian Lang, Caterina Faggio
BACKGROUND/AIMS: The thaliana phytoalexin Camalexin has been proposed for the treatment of malignancy. Camalexin counteracts tumor growth in part by stimulation of suicidal death or apoptosis of tumor cells. Similar to apoptosis of nucleated cells, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Cellular mechanisms contributing to the complex machinery executing eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, protein kinase C and caspases...
February 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28216300/boronic-acid-tethered-amphiphilic-hyaluronic-acid-derivative-based-nanoassemblies-for-tumor-targeting-and-penetration
#7
Jae Young Jeong, Eun-Hye Hong, Song Yi Lee, Jae-Young Lee, Jae-Hyoung Song, Seung-Hak Ko, Jae-Seong Shim, Sunghwa Choe, Dae-Duk Kim, Hyun-Jeong Ko, Hyun-Jong Cho
(3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and > 90% drug encapsulation efficiency were fabricated...
February 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28214868/stimulation-of-phospholipid-scrambling-of-the-erythrocyte-membrane-by-9-cis-retinoic-acid
#8
Majed Abed, Kousi Alzoubi, Florian Lang, Abdulla Al Mamun Bhuayn
BACKGROUND/AIMS: The endogenous retinoid 9-cis-retinoic acid has previously been shown to trigger apoptosis in a wide variety of cells including several tumor cells and has thus been suggested for the treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Cellular mechanisms participating in the accomplishment of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i) and formation of ceramide...
January 31, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214863/stimulation-of-erythrocyte-cell-membrane-scrambling-by-c-reactive-protein
#9
Majed Abed, Christian Thiel, Syeda T Towhid, Kousi Alzoubi, Sabina Honisch, Florian Lang, Alfred Königsrainer
BACKGROUND: Eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phosphatidylserine-translocation, is triggered by fever and inflammation. Signaling includes increased cytosolic Ca2+-activity ([Ca2+]i), caspase activation, and ceramide. Inflammation is associated with increased plasma concentration of C-reactive protein (CRP). The present study explored whether CRP triggers eryptosis. METHODS: Phosphatidylserine abundance at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ceramide abundance and caspase-3-activity utilizing FITC-conjugated antibodies...
February 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214860/stimulation-of-erythrocyte-cell-membrane-scrambling-by-adarotene
#10
Morena Mischitelli, Mohamed Jemaàa, MyriamFezai Fezai, Mustafa Almasry, Florian Lang, Caterina Faggio
BACKGROUND/AIMS: The atypical retinoid E23-(40-hydroxyl-30-adamantylbiphenyl-4-yl) acrylic acid (ST1926, adarotene) is used in the treatment of malignancy. The effect of ST1926 is at least in part due to stimulation of apoptosis. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death of erythrocytes. Hallmarks of eryptosis include cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling involved in the stimulation of eryptosis includes increase of cytosolic Ca2+ activity [Ca2+]<Sub>i</Sub>, oxidative stress and ceramide...
January 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214849/lipopeptide-induced-suicidal-erythrocyte-death-correlates-with-the-degree-of-acylation
#11
Abdulla Al Mamun Bhuyan, Minh-Thu Nguyen, Rosi Bissinger, Friedrich Götz, Florian Lang
BACKGROUND/AIMS: Consequences of bacterial infection include anemia, which could result from stimulation of suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Bacterial components known to stimulate eryptosis include lipopeptides. Signaling mediating the triggering of eryptosis include increased cytosolic Ca2+ activity ([Ca2+]<Sub>i</Sub>), oxidative stress and cellular accumulation of ceramide...
January 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213406/mitochondria-regulated-formation-of-endothelial-extracellular-vesicles-shifts-the-mediator-of-flow-induced-vasodilation
#12
Julie K Freed, Matthew J Durand, Brian Robert Hoffmann, John C Densmore, Andrew S Greene, David D Gutterman
In order to examine the effect of endothelial-derived extracellular vesicles (eEVs) on the mechanism of flow-induced dilation (FID) composition, formation, and functional effects on the mechanism of FID were examined from two different eEV subtypes, one produced from ceramide, the other from plasminogen-activator inhibitor 1 (PAI-1). Using videomicroscopy, internal diameter changes in response to increases in flow were measured in human adipose resistance arteries acutely exposed (30min) to eEVs derived from cultured endothelial cells exposed to ceramide or PAI-1...
February 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28212569/mir-124-acts-as-a-tumor-suppressor-by-inhibiting-the-expression-of-sphingosine-kinase-1-and-its-downstream-signaling-in-head-and-neck-squamous-cell-carcinoma
#13
Yuan Zhao, Zhiqiang Ling, Yubin Hao, Xiaowu Pang, Xianlin Han, Joseph A Califano, Liang Shan, Xinbin Gu
By analyzing the expression profile of microRNAs in head and neck squamous cell carcinomas (HNSCC), we found that the expression level of miR-124 was 4.59-fold lower in tumors than in normal tissues. To understand its functions, we generated a miR-124-expressing subline (JHU-22miR124) and a mock vector-transfected subline (JHU-22vec) by transfecting the mimic of miR-124 into JHU-22 cancer cells. Restored expression of miR-124 in JHU-22miR124 cells led to reduced cell proliferation, delayed colony formation, and decreased tumor growth, indicating a tumor-suppressive effect of miR-124...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28210396/multivesicular-emulsion-ceramide-containing-moisturizers-an-evaluation-of-their-role-in-the-management-of-common-skin-disorders
#14
REVIEW
Joshua A Zeichner, James Q Del Rosso
Proper stratum corneum function plays a pivotal role in maintenance of skin health, and improper function leads to skin disease. The stratum corneum is comprised of corneocytes surrounded by intercelluar lipids including ceramides, free fatty acids, and cholesterol. Ceramide predominant moisturizers have become a mainstay of treatment of skin disease. New technologies for delivery of ceramides include multivesicular emulsions, which deposit ceramides in a timerelease manner for a continuous rather than burst effect...
December 2016: Journal of Clinical and Aesthetic Dermatology
https://www.readbyqxmd.com/read/28207743/lipidomic-approach-for-stratification-of-acute-myeloid-leukemia-patients
#15
Adam Stefanko, Christian Thiede, Gerhard Ehninger, Kai Simons, Michal Grzybek
The pathogenesis and progression of many tumors, including hematologic malignancies is highly dependent on enhanced lipogenesis. De novo fatty-acid synthesis permits accelerated proliferation of tumor cells by providing membrane components but these may also alter physicochemical properties of lipid bilayers, which can impact signaling or even increase drug resistance in cancer cells. Cancer type-specific lipid profiles would permit us to monitor and interpret actual effects of lipid changes, potential fingerprints of individual tumors to be explored as diagnostic markers...
2017: PloS One
https://www.readbyqxmd.com/read/28206952/identification-of-sphingosine-kinase-1-sphk1-as-a-primary-target-of-icaritin-in-hepatocellular-carcinoma-cells
#16
Pei-Hua Lu, Min-Bin Chen, Yuan-Yuan Liu, Mian-Hua Wu, Wen-Ting Li, Mu-Xin Wei, Chao-Ying Liu, Shu-Kui Qin
Hepatocellular carcinoma (HCC) is a highly aggressive neoplasm. We aim to explore the anti-HCC activity by a natural prenylflavonoid icaritin. Icaritin was cytotoxic and pro-apoptotic when added to established (HepG2, KYN-2 and Huh-7 lines) and primary human HCC cells. At the signaling level, icaritin inhibited sphingosine kinase 1 (SphK1) activity in HCC cells, which led to pro-apoptotic ceramide production and JNK1 activation. SphK1 inhibition or silence (by shRNA/microRNA) mimicked icaritin-mediated cytotoxicity, and almost nullified icaritin's activity in HepG2 cells...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28202334/synthesis-of-specifically-deuterated-ceramide-ap-c18-and-its-biophysical-characterization-using-neutron-diffraction
#17
Stefan Sonnenberger, Adina Eichner, Thomas Hauß, Annett Schroeter, Reinhard H H Neubert, Bodo Dobner
The very heterogeneous group of ceramides is known to be mandatory for proper barrier functions of the outermost layer of mammalian skin, referred to as stratum corneum (SC). The synthesis of a specifically deuterated ceramide [AP]-C18 variant is described. The synthesized ceramide contains the racemic forms of the α hydroxy fatty acid. For the biophysical implementation, the received diastereomeric ceramide was applied in a neutron diffraction experiment. Therefore, a SC lipid model membrane was prepared containing the described ceramide (CER), cholesterol (CHOL), stearic acid (SA), and cholesterol sulfate (ChS) in a ratio of 55/25/15/5wt%...
February 12, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28198542/ceramide-synthase-2-facilitates-s1p-dependent-egress-of-thymocytes-into-the-circulation-in-mice
#18
Michael Rieck, Christiane Kremser, Katarzyna Jobin, Elisabeth Mettke, Christian Kurts, Markus Gräler, Klaus Willecke, Waldemar Kolanus
Well-defined gradients of the lipid mediator sphingosine-1-phosphate (S1P) direct chemotactic egress of mature thymocytes from the thymus into the circulation. Although it is known that these gradients result from low S1P levels in the thymic parenchyma and high S1P concentrations at the exit sites and in the plasma, the biochemical mechanisms that regulate these differential S1P levels remain unclear. Several studies demonstrated that ceramide synthase 2 (Cers2) regulates the levels of the S1P precursor sphingosine...
February 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28193314/celecoxib-mediated-activation-of-endoplasmic-reticulum-stress-induces-de-novo-ceramide-biosynthesis-and-apoptosis-in-hepatoma-hepg2-cells
#19
Hyo Jin Maeng, Jae-Hwi Song, Goon-Tae Kim, Yoo-Jeong Song, Kangpa Lee, Jae-Young Kim, Tae-Sik Park
Ceramides are the major sphingolipid metabolites involved in cell survival and apoptosis. When HepG2 hepatoma cells were treated with celecoxib, the expression of the genes in de novo sphingolipid biosynthesis and sphingomyelinase pathway was upregulated and cellular ceramide was elevated. In addition, celecoxib induced endoplasmic reticulum (ER) stress in a time-dependent manner. SPTLC2, a subunit of serine palmitoyltransferase, was overexpressed by adenovirus. Adenoviral overexression of SPTLC2 (AdSPTLC2) decreased cell viability of HEK293 and HepG2 cells...
February 10, 2017: BMB Reports
https://www.readbyqxmd.com/read/28191815/bladder-cancer-cell-growth-and-motility-implicate-cannabinoid-2-receptor-mediated-modifications-of-sphingolipids-metabolism
#20
Arianna Bettiga, Massimo Aureli, Giorgia Colciago, Valentina Murdica, Marco Moschini, Roberta Lucianò, Daniel Canals, Yusuf Hannun, Petter Hedlund, Giovanni Lavorgna, Renzo Colombo, Rosaria Bassi, Maura Samarani, Francesco Montorsi, Andrea Salonia, Fabio Benigni
The inhibitory effects demonstrated by activation of cannabinoid receptors (CB) on cancer proliferation and migration may also play critical roles in controlling bladder cancer (BC). CB expression on human normal and BC specimens was tested by immunohistochemistry. Human BC cells RT4 and RT112 were challenged with CB agonists and assessed for proliferation, apoptosis, and motility. Cellular sphingolipids (SL) constitution and metabolism were evaluated after metabolic labelling. CB1-2 were detected in BC specimens, but only CB2 was more expressed in the tumour...
February 13, 2017: Scientific Reports
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