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Galactosylceramide

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https://www.readbyqxmd.com/read/27897246/rapid-control-of-pandemic-h1n1-influenza-by-targeting-nkt-cells
#1
Bianca L Artiaga, Guan Yang, Tarun E Hutchinson, Julia C Loeb, Jürgen A Richt, John A Lednicky, Shahram Salek-Ardakani, John P Driver
Swine influenza A viruses (IAV) are a major cause of respiratory disease in pigs and humans. Currently approved anti-influenza therapies directly target the virus, but these approaches are losing effectiveness as new viral strains quickly develop drug resistance. To over come this challenge, there is an urgent need for more effective antiviral drugs. Here we tested the anti-influenza efficacy of the invariant natural killer T (NKT) cell superagonist, α-galactosylceramide (α-GalCer), which stimulates a wide array of anti-viral immune responses...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895483/improved-proliferation-of-antigen-specific-cytolytic-t-lymphocytes-using-a-multimodal-nanovaccine
#2
Bo Li, Michael Siuta, Vanessa Bright, Dmitry Koktysh, Brittany K Matlock, Megan E Dumas, Meiying Zhu, Alex Holt, Donald Stec, Shenglou Deng, Paul B Savage, Sebastian Joyce, Wellington Pham
The present study investigated the immunoenhancing property of our newly designed nanovaccine, that is, its ability to induce antigen-specific immunity. This study also evaluated the synergistic effect of a novel compound PBS-44, an α-galactosylceramide analog, in boosting the immune response induced by our nanovaccine. The nanovaccine was prepared by encapsulating ovalbumin (ova) and an adjuvant within the poly(lactic-co-glycolic acid) nanoparticles. Quantitative analysis of our study data showed that the encapsulated vaccine was physically and biologically stable; the core content of our nanovaccine was found to be released steadily and slowly, and nearly 90% of the core content was slowly released over the course of 25 days...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27864016/generation-of-antigen-specific-cytotoxic-t-lymphocytes-with-activated-b-cells
#3
Sun Ok Yun, Hee Young Shin, Chang-Yuil Kang, Hyoung Jin Kang
BACKGROUND AIMS: Dendritic cells are well known as the most potent antigen-presenting cells. Nonetheless, their use in immunotherapy has been limited by the time-consuming and laborious steps involved in their generation in vitro. Therefore, much attention has been placed on alternative antigen-presenting cells that are relatively more convenient to manipulate. METHODS: In this study, the efficacy of B cells as antigen-presenting cells, compared with dendritic cells, in the induction of cytotoxic T lymphocytes against cytomegalovirus-specific antigens was evaluated...
November 15, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27861899/sulfatide-species-with-various-fatty-acid-chains-in-oligodendrocytes-at-different-developmental-stages-determined-by-imaging-mass-spectrometry
#4
Yukie Hirahara, Taketoshi Wakabayashi, Tetsuji Mori, Taro Koike, Ikuko Yao, Masayuki Tsuda, Koichi Honke, Hitoshi Gotoh, Katsuhiko Ono, Hisao Yamada
HSO3-3-galactosylceramide (Sulfatide) species comprise the major glycosphingolipid components of oligodendrocytes and myelin and play functional roles in the regulation of oligodendrocyte maturation and myelin formation. Although various sulfatide species contain different fatty acids, it is unclear how these sulfatide species affect oligodendrogenesis and myelination. The O4 monoclonal antibody reaction with sulfatide has been widely used as a useful marker for oligodendrocytes and myelin. However, sulfatide synthesis during the pro-oligodendroblast stage, where differentiation into the oligodendrocyte lineage has already occurred, has not been examined...
November 12, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27835062/class-i-restricted-t-cell-associated-molecule-is-a-marker-for-ifn-%C3%AE-producing-inkt-cells-in-healthy-subjects-and-patients-with-type-1-diabetes
#5
Nonantzin Beristain-Covarrubias, Elsy B Canche-Pool, Carlos Ramirez-Velazquez, Juan Carlos Barragan-Galvez, Rita A Gomez-Diaz, Vianney Ortiz-Navarrete
Class I-restricted T cell-associated molecule (CRTAM) is an activation marker expressed on the cell surface of activated invariant natural killer T (iNKT) cells, CD8(+) T cells, and a small subset of CD4(+) T cells. CRTAM has also been associated with a proinflammatory profile in murine CD4(+) T cells. However, CRTAM has not been thoroughly explored in human cells. This work focused on evaluating CRTAM expression in human iNKT lymphocytes after activation with α-galactosylceramide, its widely used specific glycolipid antigen...
November 11, 2016: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/27803187/exogenous-activation-of-invariant-natural-killer-t-cells-by-%C3%AE-galactosylceramide-reduces-pneumococcal-outgrowth-and-dissemination-postinfluenza
#6
Adeline Barthelemy, Stoyan Ivanov, Maya Hassane, Josette Fontaine, Béatrice Heurtault, Benoit Frisch, Christelle Faveeuw, Christophe Paget, François Trottein
: Influenza A virus infection can predispose to potentially devastating secondary bacterial infections. Invariant natural killer T (iNKT) cells are unconventional, lipid-reactive T lymphocytes that exert potent immunostimulatory functions. Using a mouse model of postinfluenza invasive secondary pneumococcal infection, we sought to establish whether α-galactosylceramide (α-GalCer [a potent iNKT cell agonist that is currently in clinical development]) could limit bacterial superinfection...
November 1, 2016: MBio
https://www.readbyqxmd.com/read/27786470/molecular-characterization-and-anti-inflammatory-activity-of-galactosylglycerides-and-galactosylceramides-from-the-microalga-isochrysis-galbana
#7
Carolina de Los Reyes, María J Ortega, Azahara Rodríguez-Luna, Elena Talero, Virginia Motilva Sánchez, Eva Zubia
Isochrysis galbana is a marine microalga rich in PUFAs that is widely used as feed in aquaculture and more recently investigated for its potential in food applications and as source of bioactive compounds. In this study, the biomass obtained from cultures of I. galbana has been investigated to determine its content in glycosylglycerides and glycosylceramides. By using NMR, UPLC-MS/MS, and fatty acid profiles, the structures of ten monogalactosyldiacylglycerols (MGDGs 1-10) and nine digalactosyldiacylglycerols (DGDGs 11-19) have been established...
October 27, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27743499/quantifying-beta-galactosylceramide-kinetics-in-cerebrospinal-fluid-of-healthy-subjects-using-deuterium-labeling
#8
Kms Kanhai, S C Goulooze, J Stevens, J L Hay, G Dent, A Verma, T Hankemeier, T de Boer, H Meijering, J C Chavez, A F Cohen, G J Groeneveld
Therapeutics promoting myelin synthesis may enhance recovery in demyelinating diseases, such as multiple sclerosis. However, no suitable method exists to quantify myelination. The turnover of galactosylceramide (myelin component) is indicative of myelination in mice, but its turnover has not been determined in humans. Here, six healthy subjects consumed 120 mL 70% D2 O daily for 70 days to label galactosylceramide. We then used mass spectrometry and compartmental modeling to quantify the turnover rate of galactosylceramide in cerebrospinal fluid...
December 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27736245/improvement-of-neurological-disorders-in-postmenopausal-model-rats-by-administration-of-royal-jelly
#9
A Minami, H Matsushita, D Ieno, Y Matsuda, Y Horii, A Ishii, T Takahashi, H Kanazawa, A Wakatsuki, T Suzuki
OBJECTIVE: Royal jelly (RJ) from honeybees (Apis mellifera) has estrogenic activity. Estrogen deficiency after menopause leads to a high risk of memory impairment and depression as well as metabolic syndrome and osteoporosis. We here investigated the effect of RJ on memory impairment and depression-like behaviors in ovariectomized (OVX) rats. METHODS: OVX rats were administered with RJ for 82 days. Hippocampus-dependent spatial memory and depression-like behaviors were assessed by the Morris water maze test and the forced swimming test, respectively...
October 13, 2016: Climacteric: the Journal of the International Menopause Society
https://www.readbyqxmd.com/read/27721144/glycosynthase-mediated-synthesis-of-psychosine
#10
Ethan D Goddard-Borger, Christina Tysoe, Stephen G Withers
Globoid cell leukodystrophy (GCL), or Krabbe disease, is a lysosomal storage disorder characterized by a deficiency in galactosylceramidase (GALC), which hydrolyses galactosylceramide and galactosylsphingosine (psychosine). Early detection of GCL in newborns is essential for timely therapeutic intervention and could be achieved by testing infant blood samples with isotopically labeled lysosmal enzyme substrates and mass spectrometry. While isotopically labeled psychosine would be a useful tool for the early diagnosis of GCL, its synthesis is lengthy and expensive...
September 22, 2016: Carbohydrate Research
https://www.readbyqxmd.com/read/27718206/eliciting-epitope-specific-cd8-t-cell-response-by-immunization-with-microbial-protein-antigens-formulated-with-%C3%AE-galactosylceramide-theory-practice-and-protocols
#11
Pavlo Gilchuk, Frances C Knight, John T Wilson, Sebastian Joyce
CD8+ cytotoxic T lymphocytes confer protection against infectious diseases caused by viruses, bacteria, and parasites. Hence, significant efforts have been invested into devising ways to generate CD8+ T cell-targeted vaccines. Generation of microbe-free protein subunit vaccines requires a thorough knowledge of protective target antigens. Such antigens are proteolytically processed peptides presented by MHC class I molecules. To induce a robust antigen-specific CD8+ T cell response through vaccination, it is essential to formulate the antigen with an effective adjuvant...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27706127/regulatory-t-cells-decrease-invariant-natural-killer-t-cell-mediated-pregnancy-loss-in-mice
#12
L Li, J Tu, Y Jiang, J Zhou, D J Schust
Pregnancy loss is the commonest complication of pregnancy. The causes of pregnancy loss are poorly understood. It has been reported that stimulation of invariant natural killer T (iNKT) cells using α-galactosylceramide (αGC) induces pregnancy loss in mice. Here we investigated the mechanisms, especially the role of regulatory T (Treg) cells, in iNKT cell-mediated pregnancy loss. We found that injection of αGC rapidly induced fetal resorption, activated decidual iNKT cells, decreased the percentage of decidual Treg cells and their interleukin (IL)-10 and transforming growth factor (TGF)-β production, and upregulated the levels of interferon (IFN)-γ, tumor necrosis factor-α, IL-4, and IL-10 in serum...
October 5, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27698946/a-new-concept-of-enhancing-immuno-chemotherapeutic-effects-against-b16f10-tumor-via-systemic-administration-by-taking-advantages-of-the-limitation-of-epr-effect
#13
Yuting Yang, Xiaowei Tai, Kairong Shi, Shaobo Ruan, Yue Qiu, Zhirong Zhang, Bing Xiang, Qin He
The enhanced permeability and retention (EPR) effect has been comfortably accepted, and extensively assumed as a keystone in the research on tumor-targeted drug delivery system. Due to the unsatisfied tumor-targeting efficiency of EPR effect being one conspicuous drawback, nanocarriers that merely relying on EPR effect are difficult to access the tumor tissue and consequently trigger efficient tumor therapy in clinic. In the present contribution, we break up the shackles of EPR effect on nanocarriers thanks to their universal distribution characteristic...
2016: Theranostics
https://www.readbyqxmd.com/read/27697915/aglycon-diversity-of-brain-sterylglucosides-structure-determination-of-cholesteryl-and-sitosterylglucoside
#14
Hisako Akiyama, Kazuki Nakajima, Yoshiyuki Itoh, Tomoko Sayano, Yoko Ohashi, Yoshiki Yamaguchi, Peter Greimel, Yoshio Hirabayashi
To date, sterylglucosides have been reported to be present in various fungi, plants, and animals. In bacteria, such as Helicobacter pylori, proton NMR spectral analysis of isolated 1-O-cholesteryl-β-d-glucopyranoside (GlcChol) demonstrated the presence of an α-glucosidic linkage. By contrast, in animals, no detailed structural analysis of GlcChol has been reported, in part because animal-derived samples contain a high abundance of glucosylceramides (GlcCers)/galactosylceramides, which exhibit highly similar chromatographic behavior to GlcChol...
November 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27638613/zoledronate-derivatives-as-potential-inhibitors-of-uridine-diphosphate-galactose-ceramide-galactosyltransferase-8-a-combined-molecular-docking-and-dynamic-study
#15
Giovanna Pannuzzo, Adriana Carol Eleonora Graziano, Martina Pannuzzo, Marcelo Fabricio Masman, Rosanna Avola, Venera Cardile
Krabbe's disease is a neurodegenerative disorder caused by deficiency of galactocerebrosidase activity that affects the myelin sheath of the nervous system, involving dysfunctional metabolism of sphingolipids. It has no cure. Because substrate inhibition therapy has been shown to be effective in some human lysosomal storage diseases, we hypothesize that a substrate inhibition therapeutic approach might be appropriate to allow correction of the imbalance between formation and breakdown of glycosphingolipids and to prevent pathological storage of psychosine...
November 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27638608/substrate-reduction-therapy-for-krabbe-s-disease
#16
REVIEW
Scott A Sands, Steven M LeVine
Krabbe's disease (KD) is a lysosomal storage disorder in which galactosylceramide, a major glycosphingolipid of myelin, and psychosine (galactose-sphingosine) cannot be adequately metabolized because of a deficiency in galactosylceramidase. Substrate reduction therapy (SRT) has been tested in preclinical studies. The premise of SRT is to reduce the synthesis of substrates that are not adequately digested so that the substrate burden is lowered, resulting in less accumulation of unmetabolized material. SRT is used for Gaucher's disease, in which inhibitors of the terminal biosynthetic step are used...
November 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27638595/metabolic-profiling-reveals-biochemical-pathways-and-potential-biomarkers-associated-with-the-pathogenesis-of-krabbe-disease
#17
Nadav I Weinstock, Lawrence Wrabetz, M Laura Feltri, Daesung Shin
Krabbe disease (KD) is caused by mutations in the galactosylceramidase (GALC) gene, which encodes a lysosomal enzyme that degrades galactolipids, including galactosylceramide and galactosylsphingosine (psychosine). GALC deficiency results in progressive intracellular accumulation of psychosine, which is believed to be the main cause for the demyelinating neurodegeneration in KD pathology. Umbilical cord blood transplantation slows disease progression when performed presymptomatically but carries a significant risk of morbidity and mortality...
November 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27638583/krabbe-disease-one-hundred-years-from-the-bedside-to-the-bench-to-the-bedside
#18
REVIEW
David A Wenger, Mohammad A Rafi, Paola Luzi
This Review summarizes the progress in understanding the pathogenesis and treatment of Krabbe disease from the description of five patients in by Knud Krabbe until 2016. To determine the cause of this genetic disease, pathological and chemical analyses of tissues from the nervous systems of patients were performed. It was determined that these patients had a pathological feature known as globoid cell in the brain and that this consisted partially of galactosylceramide, a major sphingolipid component of myelin...
November 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27638582/lysosphingolipids-and-sphingolipidoses-psychosine-in-krabbe-s-disease
#19
REVIEW
Stefka Spassieva, Erhard Bieberich
Until recently, lipids were considered inert building blocks of cellular membranes. This changed three decades ago when lipids were found to regulate cell polarity and vesicle transport, and the "lipid raft" concept took shape. The lipid-driven membrane anisotropy in form of "rafts" that associate with proteins led to the view that organized complexes of lipids and proteins regulate various cell functions. Disturbance of this organization can lead to cellular, tissue, and organ malfunction. Sphingolipidoses, lysosomal storage diseases that are caused by enzyme deficiencies in the sphingolipid degradation pathway, were found to be particularly detrimental to the brain...
November 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27638581/my-encounters-with-krabbe-disease-a-personal-recollection-of-a-40-year-journey-with-young-colleagues
#20
Kunihiko Suzuki
In this hybrid of a personal essay and a subjective review, I am attempting to convey the sense of an adventure I myself experienced in exploring various aspects of Krabbe disease, which occupied a significant portion of my life as a biomedical researcher. This is meant to be a personal summary, and I have no pretense of this being an objective scholarly review. Since the first description of the disease by Krabbe 100 years ago, knowledge about the disease has advanced significantly. The main contributions from my laboratory, always the fruits of dedicated efforts of talented young colleagues, include the identification of the genetic defect as deficiency of galactosylceramidase, proposal of the psychosine hypothesis as the pathogenetic mechanism to explain the unique phenotypic characteristics of the disease, detailed delineations of the substrate specificities of the two lysosomal β-galactosidases, discovery of the twitcher mutant as a convenient and useful mouse model, and identification of saposin A as a specific galactosylceramide activator protein and as the second causative gene for globoid cell leukodystrophy...
November 2016: Journal of Neuroscience Research
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