1,721,058 research outputs found
Dynamics of lipid raft components during lymphocyte apoptosis: The paradigmatic role of GD3
No full textSeveral investigations have been carried out since many years in order to precisely address the function of lipid rafts in cell life and death. On the basis of the biochemical nature of lipid rafts, composed by sphingolipids, including gangliosides, sphingomyelin, cholesterol and signaling proteins, a plethora of possible interactions with various subcellular structures has been suggested. Their structural and functional role at the plasma membrane as well as in cell organelles such as endoplasmic reticulum and Golgi apparatus has been analyzed in detail in several studies. In particular, a specific activity of lipid rafts has been hypothesized to contribute to cell death by apoptosis. Although detected in various cell types, the role of lipid rafts in apoptosis has however been mostly studied in lymphocytes where the physiological apoptotic program occurs after CD95/Fas triggering. In this review, the possible contribution of lipid rafts to the cascade of events leading to T cell apoptosis after CD95/Fas ligation are summarized. Particular attention has been given to the mitochondrial raft-like microdomains, which may represent preferential sites where some key reactions can take place and can be catalyzed, leading to either survival or death of T cells. © 2007 Springer Science + Business Media, LLC
GM3 AS A TARGET OF ANTI-LYMPHOCYTIC GANGLIOSIDE ANTIBODIES IN AIDS PATIENTS
No full textIgG antibodies reacting with the GM3-comigrating band extracted from pooled AIDS lymphocytes were detected in 33.3% of AIDS patients sera, in 8% of asymptomatic anti-HIV-positive subjects, in none of the sera obtained from asymptomatic anti-HIV-negative drug abusers, from patients with acute B and chronic C hepatitis, and from healthy donors. All positive sera reacted selectively with the GM3-comigrating band obtained from AIDS lymphocytes but not with the corresponding band from normal lymphocytes. The lymphocytic ganglioside autoantigen was revealed as GM3. In addition, two main data were shown: (a) AIDS lymphocytes have an increased concentration of GM3 and (b) the ceramide of AIDS lymphocytic GM3 has a different percentual composition of fatty acids in contrast to control cells. It is suggested that these quantitative and qualitative changes might be responsible for the appearance of circulating anti-lymphocytic GM3 antibodies
Adaptor proteins a novel mechanism for the regulation of lipoprotein receptors: The case of autosomal recessive hypercholesterolemia (ARH) protein and LDLR
No full textDetection of antiphospholipid antibodies by automated chemiluminescence assay
No full textThe laboratory diagnosis of antiphospholipid antibody syndrome (APS) requires the demonstration of antiphospholipid antibodies (aPL) by lupus anticoagulant (LAC) measured through coagulation assays, anticardiolipin IgG or IgM antibodies (aCL) and/or anti-beta 2-glycoprotein I IgG or IgM antibodies (anti-beta 2-GPI), usually detected by ELISA. In this study we tested aCL by a new automated system using the chemiluminescence principle. Our results showed that, while almost all the sera from APS patients, positive for IgG aCL and anti-beta 2-GPI by ELISA, were also positive for IgG aCI by chemiluminescence, only 30.13% of patients without clinical manifestations of APS, but positive for aCL and persistently negative for anti-beta 2-GPI (by ELISA) and LA, confirmed the positive test by chemiluminescence. This difference was highly significant (p<0.0001). Interestingly, this test also prompted to identify 20% of patients positive for LA, but persistently negative for both aCL and anti-beta 2-GPI IgG (ELISA). Thus, the new technology of automated chemiluminescence assay for measuring aPL may represent an useful tool to identify "true" APS patients. (C) 2012 Elsevier B.V. All rights reserved
PrPC associates with a multimolecular complex including LRP1 and glycosphingolipids within lipid rafts
No full textThe cellular form of prion protein (PrPC) is a highly conserved cell surface GPI-anchored glycoprotein that was identified in cholesterol-enriched, detergent-resistant microdomains (‘rafts’). Like other GPI-anchored proteins, most of PrPC molecules were found in lipid rafts from neural and non-neural cells. Recently, PrPC was identified as a high-affinity receptor for Aβ oligomers. Prion protein-mediated toxicity of Aβ oligomers requires lipid rafts and the transmembrane low density lipoprotein receptor-related protein-1 (LRP1). LRP1 is an endocytic and cell-signaling receptor for diverse ligands, which control the activity of LRP1 by directing the recruited co-receptors. LRP1 controls both the surface and intracellular trafficking of PrPC in neurons. Our results show that PrPC is strictly associated with gangliosides in microdomains of neuroblastoma cells. Scanning confocal analysis reveals a consistent co-localization between PrPC and GM1, as well as between TrkA and GM1, indicating the existence of a glycosphingolipid-enriched molecular complex. These data suggest that LRP1, PrPC and TrkA may function as part of a single system associated with lipid rafts, involved in receptor-mediated neuritogenic pathway. In addition, we confirmed by co-immunoprecipitation experiments a specific PrPC -ganglioside interaction. Moreover, signal transduction experiments on neuritogenic pathway were performed using human recombinant PrP (hPrPrec), and the results indicate a role for PrPC in cell signaling in neurons. We hypothesize that the ability of PrP to induce cell signaling might involve a multi receptor complex, in which LRP1, in association with other receptors, like TrkA receptor, plays a role in signal transduction within lipid rafts.These findings suggest that PrPC associates with a multimolecular complex, including, LRP1, TrkA and ganglioside GM1, which is dependent on the integrity of lipid raft and is involved in the neuritogenic signaling and trafficking
Ganglioside GD3 as a raft component in cell death regulation
No full textSubcellular organelles such as mitochondria, endoplasmic reticulum and the Golgi complex are involved in the progression of cell death program. Recent evidence unveils that Fas ligand-mediated apoptosis induces scrambling of mitochondrial and secretory organelles via a global alteration of membrane traffic that is modulated by apical caspases. On the basis of the biochemical nature of lipid rafts, composed by sphingolipids, including gangliosides and sphingomyelin, cholesterol and signaling proteins, it has been suggested that they are part of this traffic and can participate in cell remodelling leading to cell death program execution. Although detected in various cell types, the role of lipid rafts in apoptosis has been mostly studied in T cells, where the physiological apoptotic program occurs through CD95/Fas. In this review, the possible contribution of lipid rafts to the cascade of events leading to T cell apoptosis after CD95/Fas ligation is summarized. We focused on the paradigmatic component of rafts GD3, which can proceed from the cell plasma membrane (and/or from trans Golgi network) to the mitochondria via a microtubule-dependent mechanism. This transport may be regulated by CLIPR-59, a new CLIP-170-related protein, involved in the regulation of microtubule dynamics. Particular attention has been given to mitochondrial raft-like microdomains, which may represent preferential sites where key reactions take place. Indeed, GD3, by interacting with mitochondrial raft-like microdomains, may trigger specific events involved in the apoptogenic program, including mitochondria hyperpolarization and depolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These findings introduce an additional task for identifying new molecular target(s) of anti-cancer agents
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