Search results for "Glycolipid"
showing 10 items of 38 documents
The janus face of NKT cell function in autoimmunity and infectious diseases
2018
Natural killer T cells (NKT) are a subset of T lymphocytes bridging innate and adaptive immunity. These cells recognize self and microbial glycolipids bound to non-polymorphic and highly conserved CD1d molecules. Three NKT cell subsets, type I, II and NKT-like expressing different antigen receptors (TCR) were described and TCR activation promotes intracellular events leading to specific functional activities. NKT can exhibit different functions depending on the secretion of soluble molecules and the interaction with other cell types. NKT cells act as regulatory cells in the defence against infections but, on the other hand, their effector functions can be involved in the pathogenesis of sev…
trans-C18: 1 Isomers in Cheeses Enriched in Unsaturated Fatty Acids and Manufactured with Different Milk Fat Globule Sizes
2008
International audience; Increasing the knowledge on dietary fat composition, mainly the minor components, will improve the nutritional value of foods and their labeling. In this study, we examined the trans-octadecenoic acid (C18:1) composition of Emmental cheeses enriched in unsaturated fatty acids (FA) and manufactured with milks produced by cows selected to produce small and large fat globules. The FA composition of the milks was not significantly (P > 0.05) different from the FA composition of the corresponding Emmental cheeses. Increasing the unsaturated FA content of the cheeses using dietary manipulations lead to an increase in the trans-C18:1 and changed their isomeric profiles. In …
Quantification of the Fabry marker lysoGb3 in human plasma by tandem mass spectrometry
2011
Morbus Fabry is a hereditary metabolic disorder with low prevalence and late clinical manifestation. A defect in the α-galactosidase gene leads to lysosomal accumulation of the glycolipid globotriaosylceramide (Gb3). Gb3 may be used for monitoring of enzyme replacement therapy (ERT), but diagnostic sensitivity is limited. Recently, globotriaosylsphingosine (lysoGb3) was introduced as a promising new marker with significantly better sensitivity. For Fabry diagnosis, clinical studies and possible therapy monitoring, we established a fast and reliable LC-MS/MS assay for quantification of lysoGb3 in human plasma. Protein precipitation and glycolipid extraction from EDTA plasma was performed usi…
Pharmacokinetics, pharmacodynamics, and safety of moss-aGalactosidase A in patients with Fabry disease.
2019
Moss-aGalactosidase A (moss-aGal) is a moss-derived version of human α-galactosidase developed for enzyme replacement therapy in patients with Fabry disease. It exhibits a homogenous N-glycosylation profile with >90% mannose-terminated glycans. In contrast to mammalian cell produced α-galactosidase, moss-aGal does not rely on mannose-6-phosphate receptor mediated endocytosis but targets the mannose receptor for tissue uptake. We conducted a phase 1 clinical trial with moss-aGal in six patients with confirmed diagnosis of Fabry disease during a 28-day schedule. All patients received a single dose of 0.2 mg/kg moss-aGal by i.v.-infusion. Primary endpoints of the trial were safety and pharmaco…
Treatment of Fabry's Disease With Migalastat: Outcome From a Prospective Observational Multicenter Study (FAMOUS).
2019
Fabry's disease (FD) is an X-linked lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme alpha-galactosidase A (alpha-Gal A) leading to intracellular accumulation of globotriaosylceramide (Gb3). Patients with amenable mutations can be treated with migalastat, a recently approved oral pharmacologic chaperone to increase endogenous alpha-Gal A activity. We assessed safety along with cardiovascular, renal, and patient-reported outcomes and disease biomarkers in a prospective observational multicenter study after 12 months of migalastat treatment under real-world conditions. Fifty-nine (28 females) patients (34 (57.6%) pretreated with enzyme replacement therapy) w…
Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids and evaluation of their immunomodulatory properties towards anti-tumor, anti-leishmanial and …
2019
Immunomodulatory glycolipids, among which α-galactosylceramide (KRN7000) is an iconic example, have shown strong therapeutic potential in a variety of conditions ranging from cancer and infection to autoimmune or neurodegenerative diseases. A main difficulty for those channels is that they often provoke a cytokine storm comprising both pro- and anti-inflammatory mediators that antagonize each other and negatively affect the immune response. The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously hamper…
Characterization of the interaction of the antifungal and cytotoxic cyclic glycolipopeptide hassallidin with sterol-containing lipid membranes.
2019
Hassallidins are cyclic glycolipopeptides produced by cyanobacteria and other prokaryotes. The hassallidin structure consists of a peptide ring of eight amino acids where a fatty acid chain, additional amino acids, and sugar moieties are attached. Hassallidins show antifungal activity against several opportunistic human pathogenic fungi, but does not harbor antibacterial effects. However, they have not been studied on mammalian cells, and the mechanism of action is unknown. We purified hassallidin D from cultured cyanobacterium Anabaena sp. UHCC 0258 and characterized its effect on mammalian and fungal cells. Ultrastructural analysis showed that hassallidin D disrupts cell membranes, causin…
Lateral organization of G M1 in phase-separated monolayers visualized by scanning force microscopy
2002
Phase separation of glycolipids in lipid mono- and bilayers is of great interest for the understanding of membrane function. The distribution of the ganglioside GM1 in sphingomyelin (SM)/1-palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine (POPC), SM/1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DOPC) and SM/cholesterol/POPC Langmuir-Blodgett (LB) monolayers transferred at 36 mN/m has been studied by scanning force microscopy. Besides lateral organization of the glycolipid in LB monolayers as deduced from topography, material properties have been investigated by phase imaging, pulsed force mode and force modulation microscopy. It was shown that GM1 preferentially clusters in an ordered lipid m…
Plasma glycosphingolipids in diabetics and normals
1975
In diabetic patients with hyperlipoproteinemia type IV the monohexosyl ceramide concentration in blood plasma is significantly elevated. This augmentation can be attributed to an increased monohexosyl ceramide content of the BLDL plasma fraction. In contrast, the di-, tri-, the tetrahexosyl ceramide levels remain within normal limits. In normolipidemic diabetics of comparable age, sex, and weight classes and of comparable metabolic control no elevations of glycolipid fractions could be found. However, patients with primary hyperlipoproteinemia type IV show an increase of monohexosyl ceramide concentrations in blood plasma. Therefore, the augmentation of monohexosyl ceramide levels in plasma…
Functional characterisation of alpha-galactosidase a mutations as a basis for a new classification system in fabry disease.
2013
Fabry disease (FD) is an X-linked hereditary defect of glycosphingolipid storage caused by mutations in the gene encoding the lysosomal hydrolase α-galactosidase A (GLA, α-gal A). To date, over 400 mutations causing amino acid substitutions have been described. Most of these mutations are related to the classical Fabry phenotype. Generally in lysosomal storage disorders a reliable genotype/phenotype correlation is difficult to achieve, especially in FD with its X-linked mode of inheritance. In order to predict the metabolic consequence of a given mutation, we combined in vitro enzyme activity with in vivo biomarker data. Furthermore, we used the pharmacological chaperone (PC) 1-deoxygalacto…