Search results for " RAF"
showing 10 items of 142 documents
Mechanisms of Raf-1 Kinase Inhibitor Protein Dysregulation in Triple-Negative Breast Cancers and Identification of Possible Novel Therapeutic Approac…
2014
Triple-negative breast cancers (TNBCs) are a heterogenous group of breast cancers characterized by poor prognosis because they are not amenable to targeted therapies. We have taken into account that altered expression of Raf-1 kinase inhibitor protein (RKIP), a tumor and metastasis suppressor and a promoter of drug-induced apoptosis, is frequent in TNBCs and may be involved in their aggressive biology. Interestingly, the analysis of the possible mechanisms of RKIP downregulation in TNBCs permits the identification and recapitulation of different possible approaches, including epigenetic modulation, e.g., by DNA demethylating agents or histone deacetylase inhibition, and NF-κB inhibition. Th…
Lipid rafts: a signalling platform linking lipoprotein metabolism to atherogenesis.
2012
Lipid rafts are microdomains of the plasma membrane which are enriched in cholesterol and sphingolipids. They serve as a platform for signal transduction, in particular during immune and inflammatory responses. As hypercholesterolemia and inflammation are two key elements of atherogenesis, it is conceivable that the cholesterol and cholesterol oxide content of lipid rafts might influence the inflammatory signalling pathways, thus modulating the development of atherosclerosis. In support of this emerging view, lipid rafts have been shown to be involved in several key steps of atherogenesis, such as the oxysterol-mediated apoptosis of vascular cells, the blunted ability of high density lipopr…
On ripples and rafts: Curvature induced nanoscale structures in lipid membranes
2014
We develop an elastic theory that predicts the spontaneous formation of nanoscale structures in lipid bilayers which locally phase separate between two phases with different spontaneous monolayer curvature. The theory rationalizes in a unified manner the observation of a variety of nanoscale structures in lipid membranes: Rippled states in one-component membranes, lipid rafts in multicomponent membranes. Furthermore, we report on recent observations of rippled states and rafts in simulations of a simple coarse-grained model for lipid bilayers, which are compatible with experimental observations and with our elastic model.
Modification of Plasma Membrane Organization in Tobacco Cells Elicited by Cryptogein
2014
Abstract Lipid mixtures within artificial membranes undergo a separation into liquid-disordered and liquid-ordered phases. However, the existence of this segregation into microscopic liquid-ordered phases has been difficult to prove in living cells, and the precise organization of the plasma membrane into such phases has not been elucidated in plant cells. We developed a multispectral confocal microscopy approach to generate ratiometric images of the plasma membrane surface of Bright Yellow 2 tobacco (Nicotiana tabacum) suspension cells labeled with an environment sensitive fluorescent probe. This allowed the in vivo characterization of the global level of order of this membrane, by which w…
Politi Raffaello
2010
voce bio-bibliografica su Raffaello Politi
Importance of lipid microdomains, rafts, in absorption, delivery, and biological effects of resveratrol
2013
The preventive effects of the phytoalexin trans-resveratrol toward cancer have been largely described at the cellular and molecular levels in both in vivo and in vitro models; however, its primary targets are still poorly identified. In this review, we show the crucial role of cell membrane microdomains, that is, lipid rafts, not solely in the initiation of the early biochemical events triggered by resveratrol leading to cancer cell death, but also in resveratrol absorption and distribution. Resveratrol accumulates in lipid rafts and is then taken up by cells through raft-dependent endocytosis. These events allow early activation of kinase pathways and redistribution of cell death receptors…
Absence of correlation between oxysterol accumulation in lipid raft microdomains, calcium increase, and apoptosis induction on 158N murine oligodendr…
2013
There is some evidence that oxidized derivatives of cholesterol, 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7βOHC), are increased in the plasma of patients with neurodegenerative diseases associated with demyelinization of the central nervous system (CNS). It was therefore of interest to investigate the effects of these oxysterols on oligodendrocytes, the myelin-forming cells in the CNS. To this end, 158N murine oligodendrocytes were treated with 7KC or 7βOHC inducing an apoptotic mode of cell death characterized by condensation/fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving Mcl-1, and caspase-3 activation. In contrast, under t…
7-Ketocholesterol Incorporation into Sphingolipid/Cholesterol-enriched (Lipid Raft) Domains Is Impaired by Vitamin E
2009
Cholesterol oxides, in particular 7-ketocholesterol, are proatherogenic compounds that induce cell death in the vascular wall when localized in lipid raft domains of the cell membrane. Deleterious effects of 7-ketocholesterol can be prevented by vitamin E, but the molecular mechanism involved is unclear. In this study, unlike γ-tocopherol, the α-tocopherol vitamin E form was found to prevent 7-ketocholesterol-mediated apoptosis of A7R5 smooth muscle cells. To be operative, α-tocopherol needed to be added to the cells before 7-ketocholesterol, and its anti-apoptotic effect was reduced and even suppressed when added together or after 7-ketocholesterol, respectively. Both pre- and co-treatment…
Effects of sulindac sulfide on the membrane architecture and the activity of gamma-secretase.
2007
gamma-Secretase is a membrane-embedded multi-protein complex that catalyzes the final cut of the Alzheimer's disease-related amyloid precursor protein (APP) to amyloid-beta peptides of variable length (37-43 amino acids) via an unusual intramembrane cleavage. Recent findings propose that some commonly used non-steroidal anti-inflammatory drugs (NSAIDs) have the ability to modulate specifically gamma-secretase activity without inhibiting the enzyme as a whole. These drugs may shift the processing of APP from the longer amyloid-beta 42 peptide towards shorter, less fibrillogenic and less toxic amyloid-beta species. We hypothesize that gamma-secretase activity, as an enzyme that is strictly as…
Perturbed interactions of mutant proteolipid protein/DM20 with cholesterol and lipid rafts in oligodendroglia: implications for dysmyelination in spa…
2006
Missense mutations in the humanPLP1gene lead to dysmyelinating diseases with a broad range of clinical severity, ranging from severe Pelizaeus–Merzbacher disease (PMD) to milder spastic paraplegia type 2 (SPG-2). The molecular pathology has been generally attributed to endoplasmic reticulum (ER) retention of misfolded proteolipid protein (PLP) (and its splice isoform DM20) and induction of the unfolded protein response. As opposed to previous studies of heterologous expression systems, we have analyzed PLP/DM20 trafficking in oligodendroglial cells, thereby revealing differences between PMD and SPG-2-associated PLP/DM20 isoforms. PLPA242Vand DM20A242V(jimpy-msdin mice), associated with seve…