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Neisseria gonorrhoeae that infect men have lipooligosaccharides with terminal N-acetyllactosamine repeats.

Infectious Neisseria gonorrhoeae make relatively large lipooligosaccharides (LOS) that structurally resemble human glycosphingolipids. MS11mkC is an LOS variant of N. gonorrhoeae strain MS11 which was isolated from men at the onset of dysuria (Schneider, H., Griffiss, J. M., Boslego, J. W., Hitchcock, P. J., Zahos, K. M., and Apicella, M. A. (1991) J. Exp. Med. 174, 1601-1605). Delayed extraction matrix-assisted laser desorption and ionization and electrospray ionization mass spectrometry of O-deacylated MS11mkC LOS produced ions consistent with known LOS which have lacto-N-neotetraose (Galbet…

Enzymological diagnosis of a group of lysosomal storage diseases. Review of 5-year experience of 1600 patient-sample referrals.

Lysosomal acid hydrolase activities have been measured in extracts of peripheral blood leucocytes of approximately 1600 patients referred from throughout Australia, each of whom was suspected of having a neurolipidosis. Assays for 12 different lysosomal enzymes were performed on each patient as a routine; ten assay systems were based on commercially available substrates, and four used radiolabelled glycosphingolipids prepared in our own laboratory. Of the 85 patients with positive results, 81 were diagnosed as being homozygous-deficient for a particular lysosomal enzyme. These patients compris…

Impact of glycolipid particles in fetal bovine serum on the flow cytometric detection of cell-surface SSEA-4.

We recently established a flow cytometer assay that can detect the interaction between antibodies and glycolipid antigens present on lipid vesicles such as liposomes and extracellular vesicles. Using this system, we detected particles reactive with an anti-stage-specific embryonic antigen-4 (SSEA-4) antibody (MC813-70) in fetal bovine serum (FBS). SSEA-4 is a carbohydrate antigen also known as sialyl-Gb5 glycosphingolipid and is widely used as a marker of human stem cells. We detected an SSEA-4-reactive signal in precipitated particles obtained by centrifugation of FBS by 10,000g (10KgP). Howe

Novel glycan-related biomarker discovery by total glycomic and focused protein glycomic analyses.

The cell surface is covered with a variety of glycan subtypes (sub-glycans) such as N-glycans, O-glycans, glycosphingolipid-glycans, and glycosaminoglycans, which are collectively called the glycocalyx. The expression patterns of sub-glycans change in response to various biological events during disease pathogenesis; however, the structures of all major sub-glycans and their relative concentrations in a cell have been hardly reported. Total glycomic analysis, which comprehensively measures all major sub-glycans, is a powerful tool to discover cellular and clinical biomarkers. In this review, w

Ophthalmic Manifestations in Fabry Disease: Updated Review.

Fabry disease (FD) is an X-linked lysosomal storage disorder, causing Gb-3 (globotriaosylceramide) buildup in cellular lysosomes throughout the body, in particular in blood vessel walls, neuronal cells, and smooth muscle. The gradual accumulation of this glycosphingolipid in numerous eye tissues causes conjunctival vascular abnormalities, corneal epithelial opacities (cornea verticillata), lens opacities, and retinal vascular abnormalities. Although a severe vision impairment is rare, these abnormalities are diagnostic indicators and prognostics for severity. Cornea verticillata is the most co

Raft-like membranes from the trans-Golgi network and endosomal compartments.

This article describes a procedure to prepare a raft-like intracellular membrane fraction enriched for the trans-Golgi network (TGN) and endosomal compartments. The initial step in this technique involves cell disruption by homogenization, followed by clearance of the plasma membrane, late endosomes, mitochondria and the endoplasmic reticulum by differential sedimentation. Carbonate treatment, sonication and sucrose density-gradient ultracentrifugation are subsequently used to isolate the target membranes. The isolated subcellular fraction contains less than 1% of the total cellular proteins,

Small-molecule therapeutics for the treatment of glycolipid lysosomal storage disorders.

Glycosphingolipid (GSL) lysosomal storage disorders are a small but challenging group of human diseases to treat. Although these disorders appear to be monogenic in origin, where the catalytic activity of enzymes in GSL catabolism is impaired, the clinical presentation and severity of disease are heterogeneous. Present attitudes to treatment demand individual therapeutics designed to match the specific disease-related gene defect; this is an acceptable approach for those diseases with high frequency, but it lacks viability for extremely rare conditions. An alternative therapeutic approach term

Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process.

The protective antigen (PA) of the anthrax toxin binds to a cell surface receptor and thereby allows lethal factor (LF) to be taken up and exert its toxic effect in the cytoplasm. Here, we report that clustering of the anthrax toxin receptor (ATR) with heptameric PA or with an antibody sandwich causes its association to specialized cholesterol and glycosphingolipid-rich microdomains of the plasma membrane (lipid rafts). We find that although endocytosis of ATR is slow, clustering it into rafts either via PA heptamerization or using an antibody sandwich is necessary and sufficient to trigger ef

Mannosylinositol Phosphorylceramide Biosynthesis Is Required for Cell Surface Adaptation to Ethanol Stress in Saccharomyces cerevisiae.

Saccharomyces cerevisiae exhibits a remarkable ability to tolerate high concentrations of ethanol during fermentation, yet the molecular basis underlying this adaptive trait remains incompletely understood. Here, we identify the biosynthesis of the complex sphingolipid mannosylinositol phosphorylceramide (MIPC) as a key determinant of ethanol tolerance in S. cerevisiae. Cells lacking the MIPC synthases Csg1 and Csh1 exhibited pronounced ethanol hypersensitivity and loss of viability. This defect was associated with impaired maintenance of cell wall integrity under ethanol stress and was furthe

Glycolipidomics of Liver Flukes and Host Tissues during Fascioliasis: Insights from Mass Spectrometry Imaging.

Fascioliasis, a zoonotic disease caused by liver flukes of the genus Fasciola, poses significant health threats to both humans and livestock … MALDI MSI) and nanohydrophilic interaction chromatography tandem mass spectrometry, we investigated glycosphingolipids (GSLs) in both adult and immature parasite stages as well as the host liver and bile duct to unravel the intricacies of the host-pathogen interplay and associated pathology. Several GSLs showed characteristic distribution patterns within the parasit …

Mitogenic response of near-diploid mouse cell line m5S/1M induced by epidermal growth factor.

A nonmalignant near-diploid cell line m5s/1M, established by Sasaki and Kodama (J. Cell. Res., 131:114-122, 1987), was shown to respond to the epidermal growth factor (EGF). The m5s/1M cells showed high sensitivity to post-confluence inhibition of cell division and formed a uniform monolayer after the cells had become confluent. The addition of EGF resulted in loss of contact-dependent inhibition of growth and caused a massive piling up of a multilayered array of cells after they had become confluent. When EGF was removed from the medium, the cell number decreased rapidly, and the cells formed

Emerging role of ceramides and other sphingolipids in atherosclerosis.

Atherosclerotic cardiovascular disease (ASCVD) remains the foremost cause of mortality worldwide. Despite the proven efficacy of statins and … (HDL)-associated chaperones. We further discuss how complex sphingolipids-such as sphingomyelin and glycosphingolipids-influence lesion initiation and progression. By elucidating the interplay between these lipid mediators and the vascular and immune cells in the atheroma, this review highlights the sphingolipid metabolic network as a promising source of therapeutic …

Inflammation and autophagy impairment in presymptomatic pediatric patients with Fabry disease identified by newborn screening.

BACKGROUND: Fabry disease (FD) is a lysosomal storage disorder caused by a deficiency of α-galactosidase A. Although the accumulation of glycosphingolipids occurs very early, clinical manifestations are often delayed. Little is known about the cellular changes that occur in the presymptomatic phase and may progressively cause damage. To this aim, we evaluated inflammatory markers, cellular stress, and autophagy in presymptomatic pediatric patients with FD identified through newborn screening. METHODS: We conducted a cross-sectional study of 12 male presymptomatic FD patients with a mean age o…

Ganglioside therapy in cancer molecular insights and therapeutic opportunities.

Gangliosides, a class of glycosphingolipids located on the plasma membrane of nearly all cells, play a crucial role in cell signaling and lipid raft dynamics. Their expression is notably high during embryonic development, markedly reduced in most adult tissues, but significantly elevated in various tumor tissues. This distinct expression pattern highlights gangliosides as promising therapeutic targets due to their roles in tumor progression, metastasis, and therapeutic resistance. Targeted ganglioside therapies, particularly monoclonal antibodies against GD2, have already demonstrated clinical…

Множественный метод ЛК-МС/МС для количественной оценки 14 сфинголипидов в организме человека с цереброспином (CSF).

Сфинголипиды представляют собой биоактивные липиды, состоящие из сфингоидной основы, связанной с различными длинноцепными толстыми кислотами и фосфохолином, и в некоторых случаях могут также содержать один или несколько сахаров. Несколько видов сфинголипидов имеют схожие структуры и даже могут иметь идентичный химический состав, но различаются по своей биологической функции. По этой причине их можно точно определить только с использованием жидкой хроматографии в сочетании с масс-спектрометрией (LC-MS). Этот метод может отделять сфинголипиды на основе их гидрофобии и давать количественную оценк

Совпадение в аннотации оригинала
Sphingolipids are bioactive lipids comprised of a sphingoid base linked to various long-chain fatty acids and phosphocholine and, in some ca … o measure 14 sphingolipid species, including 7 ceramides (C14, C16, C18, C20, C24, C18:1, C24:1), 4 glycosphingolipids (C16 Glucosyl(ß) Ceramide (d18:1/16:0, C16 Galactosyl(ß) Ceramide (d18:1/16:0), C16 Lac Cer, C18 Lac Cer) and 3 sphingosines (Sphingosine (Sph), Glucosyl(ß) Sphingosine (d18:1), Galactosyl(ß) Sphingosine (d18:1)) in human cerebrospinal fluid (CSF). …

Human in vitro models for Fabry disease: new paths for unravelling disease mechanisms and therapies.

Fabry disease is a multi-organ disease, caused by mutations in the GLA gene and leading to a progressive accumulation of glycosphingolipids due to enzymatic absence or malfunction of the encoded alpha-galactosidase A. Since pathomechanisms are not yet fully understood and available treatments are not efficient for all mutation types and tissues, further research is highly needed. This research involves many different model types, with significant effort towards the establishment of an in vivo model. However, these models did not replicate the variety of symptoms observed in patients. As an alt…

Beneficial in vitro effect of N-acetylcysteine and coenzyme Q10 on DNA damage in neurodegenerative Niemann-Pick type C 1 disease: preliminary results.

Niemann-Pick type C1 (NP-C1) is a lysosomal storage disease (LSD) caused by mutations in NPC1 gene that lead to defective synthesis of the respective lysosomal transporter protein and cholesterol accumulation in late endosomes/lysosomes (LE/L) compartments, as well as glycosphingolipids GM2 and GM3 in the central nervous system (CNS). Clinical presentation varies according to the age of onset and includes visceral and neurological symptoms, such as hepatosplenomegaly and psychiatric disorders. Studies have been associating the pathophysiology of NP-C1 with oxidative damage to lipids and protei…

Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations.

Fabry Disease (FD) is a rare lysosomal storage disorder caused by mutations in the GLA gene on the X chromosome, leading to a deficiency in α-galactosidase A (AGAL) enzyme activity. This leads to the accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3), in vital organs such as the kidneys, heart, and nervous system. While FD was initially considered predominantly affecting males, recent studies have uncovered that heterozygous Fabry women, carrying a single mutated GLA gene, can manifest a wide array of clinical symptoms, challenging the notion of asymptomatic carriers. Th…

Repurposing Amphotericin B and Its Liposomal Formulation for the Treatment of Human Mpox.

Mpox (monkeypox) is a zoonotic viral disease caused by the mpox virus (MPXV). Recently in 2022, a multi-country Mpox outbreak has determined … st-cell lipid rafts are small, highly dynamic plasma-membrane microdomains enriched in cholesterol, glycosphingolipids and phospholipids that have emerged as crucial surface-entry platforms for several viruses. We previously demonstrated that the antifungal drug Amphotericin B (AmphB) inhibits fungal, bacterial and viral infection of host cells through its capacity …