Search results for "CERAMIDE"
showing 10 items of 94 documents
Cross-talk between phosphatidic acid and ceramide during ethanol-induced apoptosis in astrocytes
2005
Background Ethanol inhibits proliferation in astrocytes, an effect that was recently linked to the suppression of phosphatidic acid (PA) formation by phospholipase D (PLD). The present study investigates ethanol's effect on the induction of apoptosis in astrocytes and the formation of ceramide, an apoptotic signal. Evidence is presented that the formation of PA and ceramide may be reciprocally linked during ethanol exposure. Results In cultured rat cortical astrocytes, ethanol (0.3–1 %, v/v) induced nuclear fragmentation and DNA laddering indicative of apoptosis. Concomitantly, in cells prelabeled with [3H]-serine, ethanol caused a dose-dependent, biphasic increase of the [3H]-ceramide/ [3H…
Goodpasture antigen-binding protein, the kinase that phosphorylates the goodpasture antigen, is an alternatively spliced variant implicated in autoim…
2000
The non-collagenous C-terminal domain of the alpha(3) chain of collagen IV is the autoantigen in Goodpasture disease, an autoimmune disorder described only in humans. Specific N-terminal phosphorylation is a biological feature unique to the human domain when compared with other homologous domains lacking immunopathogenic potential. We have recently cloned from a HeLa-derived cDNA library a novel serine/threonine kinase (Goodpasture antigen-binding protein (GPBP)) that phosphorylates the N-terminal region of the human domain (Raya, A. Revert, F, Navarro, S. and Saus J. (1999) J. Biol. Chem. 274, 12642-12649). We show here that the pre-mRNA of GPBP is alternatively spliced in human tissues an…
The longevity assurance homologue of yeast lag1 (Lass) gene family (Review)
2009
The Lass gene family contains a group of highly conserved genes that are found in eukaryotic species. The founding member, lag1, was discovered in a screen for yeast longevity genes. Subsequently, lag1 homologs were discovered in other organisms including six mammalian paralogs. All Lass genes encode a highly conserved Lag1 domain and many also have an additional Hox domain. Lass proteins are ceramide synthases and therefore are critical for ceramide biosynthesis. Ceramide synthase is also a critical enzyme in the sphingolipid biosynthetic pathway. As ceramide and sphingolipids are key intermediates in diverse cellular processes such as cell growth, apoptosis, and stress response and may al…
Pivotal advance: alpha-galactosylceramide induces protection against lipopolysaccharide-induced shock.
2007
Abstract α−galactosylceramide, a natural killer T cell ligand, and its synthetic homolog, KRN7000, consistently influence IFN-γ and TNF-α release, both mediators of LPS-induced shock. To modify the course of endotoxin shock, we injected KRN7000 at different time points of experimental systemic Shwartzman reaction. Mice treated with KRN7000 survived when it was injected within 2 h before and after LPS challenge. Mice survival was associated with low levels of T helper 1 (Th1) cytokines, such as IFN-γ and TNF-α. By contrast, protection from endotoxin shock was associated with an increase of T helper 2 (Th2) cytokines, like IL-4 and IL-10. A role of Th2 cytokines in counteracting LPS-induced s…
Prophylaxis of lipopolysaccharide-induced shock by α-galactosylceramide
2008
AbstractThe NKT cell ligand α-galactosylceramide and its synthetic homologue KRN7000 stimulate rapid and copious secretion of IFN-γ and TNF-α release, both of which are key mediators of LPS-induced shock. We showed that KRN7000, injected before or within 2 h after LPS challenge, was able to prevent endotoxic shock. KRN7000 induced survival when the mice were injected 6, 9, or 12 days before the first injection of LPS, and this protective effect was associated with reduction upon subsequent challenge in the levels of IFN-γ, TNF-α, MCP-1, and an increase of IL-10. Further analysis showed that the animals treated with KRN7000 prior to LPS challenge had lower numbers of F4/80+, NKT, and NK cell…
Lipidomic profiling identifies signatures of metabolic risk
2020
Background: Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors. Methods: We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations with obesity, dysglycemia, and dyslipidemia. Independent external validation was sought in three independent cohorts. Follow-up data from the FHS were used to test for lipid metabolites associated with longitudinal changes in metabolic risk factors. Results: Thirty-nine lipids were…
Plasma Ceramides, Mediterranean Diet, and Incident Cardiovascular Disease in the PREDIMED Trial
2017
Background: Although in vitro studies and investigations in animal models and small clinical populations have suggested that ceramides may represent an intermediate link between overnutrition and certain pathological mechanisms underlying cardiovascular disease (CVD), no prospective studies have investigated the association between plasma ceramides and risk of CVD. Methods: The study population consisted of 980 participants from the PREDIMED trial (Prevención con Dieta Mediterránea), including 230 incident cases of CVD and 787 randomly selected participants at baseline (including 37 overlapping cases) followed for ≤7.4 years. Participants were randomized to a Mediterranean diet supplemente…
Determination of globotriaosylceramide in plasma and urine by mass spectrometry
2009
Abstract Background: Fabry disease is an X-chromosomally inherited lysosomal storage disorder leading to accumulation of glycosphingolipids, mainly globotriaosylceramide (ceramide-trihexoside, Gb3). Concentrations of Gb3 in plasma and urine have been used to diagnose Fabry disease and to monitor enzyme replacement therapy with recombinant α-galactosidase. Methods: Gb3 was purified from plasma or urine by combined liquid extraction/protein precipitation and solid-phase extraction, and was detected by flow-injection analysis electrospray mass spectrometry (MS) using multi-reaction-monitoring. Calibration was performed via standard addition using C17-Gb3 as internal standard. The most abundant…
Ceramide inhibits Kv currents and contributes to TP-receptor-induced vasoconstriction in rat and human pulmonary arteries
2011
et al.
Cutaneous complications of Anderson-Fabry disease.
2013
Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by a defect in the -galactosidase A gene, which leads to the deficiency of the hydrolytic enzyme -galactosidase A. The consequent inability to catabolize glycosphingolipids causes progressive accumulation of globotriaosylceramide in the vascular endothelium throughout the body. Fatalities in the classical phenotype may usually occur as a consequence of cerebral, cardiac or renal disease. Dermatological manifestations are a relevant feature of Fabry disease and include angiokeratomas, telangiectasiae, lymphedema, anhidrosis or hypohidrosis and pseudo-acromegalic facial appearance. The actual causal treatment for Fabry …