Search results for "Sphingolipids"
showing 10 items of 39 documents
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…
Sulfatide excreting heterozygous carrier of juvenile metachromatic leukodystrophy or asymptomatic patient of adult metachromatic leukodystrophy.
1975
In a family with juvenile metachromatic leukodystrophy (sulfatide lipidosis) 2 patients showed residual arysulfatase A activities of 5--6%. The patients' healthy father was characterized biochemically by a 39% normal activity of leukocyte plus plasma arylsulfatase A. The father was further characterized by a high sulfatide excretion (0.2--0.5 mg/I urine) and, paradoxically, by a normal sulfatide degrading enzyme activity in vitro. This special carrier is suspected to be heterozygous for a) arylsulfatase A deficiency and b) arylsulfatase A (sulfatidase) lability. This presumed additional genetic defect could be the cause of the sulfatide excretion which, in turn, would be a sign of the precl…
Long-lived Humans Have a Unique Plasma Sphingolipidome
2021
A species-specific lipidome profile is an inherent feature linked to longevity in the animal kingdom. However, there is a lack of lipidomic studies on human longevity. Here, we use mass spectrometry-based lipidomics to detect and quantify 151 sphingolipid molecular species and use these to define a phenotype of healthy humans with exceptional life span. Our results demonstrate that this profile specifically comprises a higher content of complex glycosphingolipids (hexosylceramides and gangliosides), and lower levels of ceramide species from the de novo pathway, sphingomyelin and sulfatide; while for ceramide-derived signaling compounds, their content remains unchanged. Our findings suggest …
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…
alpha GalNAc is essential for recognition of Exo-1 epithelial antigen by mouse monoclonal antibody Pa-G-14.
1993
Mouse monoclonal antibody Pa-G-14 detects Exo-1, an antigen whose expression is regulated in the processes of epithelial-cell differentiation and transformation. The epitope recognized by Pa-G-14 is present both in glycosphingolipids and in mucin glycoproteins. To characterize the specificity of Pa-G-14, immuno-thin-layer chromatography, biochemical, and enzymatic treatment of glycosphingolipid extracts from human pancreas were used. The antibody bound to all blood-group-A substances; alpha GalNAc, but not fucose, was essential for reactivity. In ELISA, Pa-G-14 also reacted with ovine and bovine submaxillary mucins but not with porcine submaxillary mucin. Binding to ovine submaxillary mucin…
SPHINGOLIPID TRANSPORT FROM THE TRANSGOLGI NETWORK TO THE APICAL SURFACE IN PERMEABILIZED MDCK CELLS
1992
AbstractWe have measured the transport of de novo synthesized fluorescent analogs of sphingomyelin and glucosylceramide from the trans-Golgi network (TGN) to the apical membrane in basolaterally permeabilized Madin-Darby canine kidney (MDCK) cells. Sphingolipid transport was temperature, ATP and cytosol dependent. Introduction of bovine serum albumin (BSA), which binds fluorescent sphingolipid monomer, into the permeabilized cells, did not affect lipid transport to the apical membrane. Both fluorescent sphingomyelin and glucosylceramide analogs were localized to the lumenal bilayer leaflet of isolated TGN-derived vesicles. These results strongly suggest that both sphingolipids are transport…
Oligomerization of Vibrio cholerae cytolysin yields a pentameric pore and has a dual specificity for cholesterol and sphingolipids in the target memb…
1999
Vibrio cholerae cytolysin permeabilizes animal cell membranes. Upon binding to the target lipid bilayer, the protein assembles into homo-oligomeric pores of an as yet unknown stoichiometry. Pore formation has been observed with model liposomes consisting of phosphatidylcholine and cholesterol, but the latter were much less susceptible to the cytolysin than were erythrocytes or intestinal epithelial cells. We here show that liposome permeabilization is strongly promoted if cholesterol is combined with sphingolipids, whereby the most pronounced effects are observed with monohexosylceramides and free ceramide. These two lipid species are prevalent in mammalian intestinal brush border membranes…
Mechanism of action of sphingolipids and their metabolites in the toxicity of fumonisin B1.
2005
Fumonisins are a group of mycotoxins produced primarily by Fusarium moniliforme. Several fumonisins have been isolated through out the years but only fumonisin B1, B2 and B3 are the ones present in naturally contaminated foods, with B1 being the most toxic between them. The structural similarity between sphinganine and fumonisin B1 suggests that the mechanism of action of this mycotoxin is mainly via disruption of sphingolipid metabolism, this is an important step in the cascade of events leading to altered cell growth, differentiation and cell injury. Sphingolipids are a second type of lipid found in cell membranes, particularly nerve cells and brain tissues. Toxicity of fumonisin B1 is gi…
Apprehending ganglioside diversity: a comprehensive methodological approach
2015
Gangliosides make a wide family of glycosphingolipids ubiquitously expressed in mammalian tissues and particularly abundant in the brain and nervous system. They exhibit a huge diversity due to structural variations in both their oligosaccharidic chain and ceramide moiety, which represent a real analytical challenge. Since their discovery in the 1940s, methods have persistently improved until the emergence of Liquid Chromatography/Mass Spectrometry (LC/MS) which offers a high level of specificity and sensitivity and is suitable with high-throughput profiling studies. We describe here a comprehensive approach relying on various techniques and aiming at fully characterizing gangliosides in bi…