Search results for "oxysterol"
showing 10 items of 37 documents
Muricholic Acids Promote Resistance to Hypercholesterolemia in Cholesterol-Fed Mice
2021
International audience; Background and aims: Hypercholesterolemia is a major risk factor for atherosclerosis and cardiovascular diseases. Although resistant to hypercholesterolemia, the mouse is a prominent model in cardiovascular research. To assess the contribution of bile acids to this protective phenotype, we explored the impact of a 2-week-long dietary cholesterol overload on cholesterol and bile acid metabolism in mice. Methods: Bile acid, oxysterol, and cholesterol metabolism and transport were assessed by quantitative real-time PCR, western blotting, GC-MS/MS, or enzymatic assays in the liver, the gut, the kidney, as well as in the feces, the blood, and the urine. Results: Plasma tr…
Impact of 7-Ketocholesterol and Very Long Chain Fatty Acids on Oligodendrocyte Lipid Membrane Organization: Evaluation Via LAURDAN and FAMIS Spectral…
2011
International audience; In the context of multiple sclerosis and X-linked adrenoleukodystrophy, 7-ketocholesterol (7KC) and very long chain fatty acids (C24:0, C26:0) are supposed to induce side effects respectively on oligodendrocytes which are myelin (which is a lipoproteic complex) synthesizing cells. The effects of 7KC (25, 50 mu M), C24:0 and C26:0 (10, 20 mu M) on cell viability and lipid membrane organization were investigated on 158N murine oligodendrocytes. Concerning 7KC and fatty acids (at 20 mu M only):1) cell growth was strongly inhibited; 2) marked induction of cell death was revealed with propidium iodide (PI); 3) no apoptotic cells were found with C24:0 and C26:0 (absence of…
Phytosterols: to be or not to be toxic; that is the question
2008
Plant sterols (phytosterols) are membrane constituents of all plants with a structure analogous to that of cholesterol. Thus, phytosterols have either an additional methyl or ethyl group on the carbon-24 position or an additional double bond in the side chain (1) . Noteworthy, in patients with the rare inherited disease of phytosterolaemia characterized by a hyperabsorption and diminished biliary secretion of cholesterol and phytosterols as well as by tendon and tuberous xanthoma, elevated plasma concentrations of phytosterols (campesterol, sitosterol) have been shown to constitute a risk factor for premature atherosclerosis (2) . However, whether plasma concentrations of campesterol and si…
Pro-oxidant effects of 7-hydroperoxycholest-5-en-3β-ol on the copper-initiated oxidation of low density lipoprotein
1995
AbstractIn low density lipoproteins (LDL) supplemented with aged cholesterol and oxidized in the presence of Cu2+, an increase of the lipid oxidation parameters was observed compared with pure cholesterol-enriched LDL. A compound, identified as 7-hydroperoxycholesterol (7HPC), isolated from aged cholesterol and added to LDL, reproduced the above effects. The results indicate that the pro-oxidant effect of 7HPC is dependent on the hydroperoxy group since the corresponding alcohol derivative, 7α-hydroxycholesterol, had no such effect. These data suggest that among the LDL-associated lipid peroxides, cholesterol peroxides may have important implications in the susceptibility of this lipoprotei…
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…
modifications peroxysomales associées à l'oxyapoptophagie induite par le 7-cétocholestérol et identification de lipides cytoprotecteurs
2020
Oxidative stress is often increased in several diseases such as age-related diseases (cardiovascular diseases, eye diseases (age-related macular degeneration (AMD) and cataracts), neurodegenerative diseases (Alzheimer's disease, multiple sclerosis), chronic inflammatory diseases (chronic inflammatory bowel disease (IBD)) as well as certain rare genetic diseases (Niemann Pick's disease, X-linked adrenoleukodystrophy (X-ALD)). Oxidative stress can oxidize various molecules, in particular the cholesterol present in lipid membranes, and lead to the formation of oxidized cholesterol derivatives: oxysterols. Some of them, such as 7-ketocholesterol (7KC), are toxic and may be the cause of a type o…
Contribution of Cholesterol and Oxysterols in the Physiopathology of Cataract: Implication for the Development of Pharmacological Treatments
2010
The development of cataract is associated with some lipid changes in human lens fibers, especially with increased accumulation and redistribution of cholesterol inside these cells. Some direct and indirect lines of evidence, also suggest an involvement of cholesterol oxide derivatives (also named oxysterols) in the development of cataract. Oxysterol formation can result either from nonenzymatic or enzymatic processes, and some oxysterols can induce a wide range of cytotoxic effects (overproduction of reactive oxygen species (ROS); phospholipidosis) which might contribute to the initiation and progression of cataract. Thus, the conception of molecules capable of regulating cholesterol homeos…
Prevention of 7-ketocholesterol-induced side effects by natural compounds
2018
Cholesterol oxidation products, also named oxysterols, can be formed either by cholesterol auto-oxidation, enzymatically or both. Among these oxysterols, 7-ketocholesterol (7KC) is mainly formed during radical attacks that take place on the carbon 7 of cholesterol. As increased levels of 7KC have been found in the tissues, plasma and/or cerebrospinal fluid of patients with major diseases, especially age-related diseases (cardiovascular diseases, eye diseases, neurodegenerative diseases), some cancers, and chronic inflammatory diseases, it is suspected that 7KC, could contribute to their development. Since 7KC, provided by the diet or endogenously formed, is not or little efficiently metabol…
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…
Phospholipidosis and down-regulation of the PI3-K/PDK-1/Akt signalling pathway are vitamin E inhibitable events associated with 7-ketocholesterol-ind…
2007
International audience; Among the oxysterols accumulating in atherosclerotic plaque, 7-ketocholesterol (7KC) is a potent apoptotic inducer, which favours myelin figure formation and polar lipid accumulation. This investigation performed on U937 cells consisted in characterizing the myelin figure formation process; determining the effects of 7KC on the PI3-K/PDK-1/Akt signalling pathway; evaluating the activities of vitamin E (Vit-E) (α-tocopherol) on the formation of myelin figures and the PI3-K/PDK-1/Akt signalling pathway and assessing the effects of PI3-K inhibitors (LY-294002, 3-methyladenine) on the activity of Vit-E on cell death and polar lipid accumulation. The ultrastructural and b…