Search results for "Phospholipidosis"
showing 8 items of 8 documents
A lipidomic cell-based assay for studying drug-induced phospholipidosis and steatosis
2017
Phospholipidosis and steatosis are two toxic effects, which course with overaccumulation of different classes of lipids in the liver. MS-based lipidomics has become a powerful tool for the comprehensive determination of lipids. LC-MS lipid profiling of HepG2 cells is proposed as an in vitro assay to study and anticipate phospholipidosis and steatosis. Cells with and without pre-incubation with a mixture of free fatty acids (FFA) (i.e., oleic and palmitic) were exposed to a set of well-known steatogenic and phospholipidogenic compounds. The use of FFA pre-loading accelerated the accumulation of phospholipids thus leading to a better discrimination of phospholipidosis, and magnified the lipid…
Caractérisation des figures myéliniques associées à l'accumulation de lipides polaires induites par différents oxystérols cytotoxiques identifiés dan…
2006
Atherosclerosis is a complex and chronic arterial process which is characterized by a remodeling of the vascular wall, associated with inflammatory reactions, proliferation and cell death process, and with accumulation of oxidized lipids among which oxysterols (cholesterol oxidation products) which might play key roles in the initiation and development of atheromatous lesions. Our work performed on U937 and THP1 promonocytic cells, rat aorta embryonic A7R5 cells, and breast carcinoma MCF7 cells (caspase-3 deficient). Different oxysterols, present in large quantity in atheromatous lesions, were used: 7-cétocholestérol (7KC), 7Β-hydroxycholestérol, 25-hydroxycholestérol, cholestérol-5Α, 6Α-ep…
A metabolomics cell-based approach for anticipating and investigating drug-induced liver injury
2016
AbstractIn preclinical stages of drug development, anticipating potential adverse drug effects such as toxicity is an important issue for both saving resources and preventing public health risks. Current in vitro cytotoxicity tests are restricted by their predictive potential and their ability to provide mechanistic information. This study aimed to develop a metabolomic mass spectrometry-based approach for the detection and classification of drug-induced hepatotoxicity. To this end, the metabolite profiles of human derived hepatic cells (i.e., HepG2) exposed to different well-known hepatotoxic compounds acting through different mechanisms (i.e., oxidative stress, steatosis, phospholipidosis…
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…
Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activi…
2009
Oxysterols resulting from spontaneous or enzymatic oxidation of cholesterol are present in numerous foodstuffs and have been identified at increased levels in the plasma and the vascular walls of patients with cardiovascular diseases, especially in atherosclerotic lesions. Consequently, their role in lipid disorders is widely suspected, but they may also contribute to the development of important degenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, osteoporosis, age-related macular degeneration, and cataract. Since these pathologies can be associated with the presence of apoptotic cells, oxidative and inflammatory processes, and lipid disorders, the ab…
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…
Side effects of oxysterols: cytotoxicity, oxidation, inflammation, and phospholipidosis.
2008
Oxysterols are 27-carbon atom molecules resulting from autoxidation or enzymatic oxidation of cholesterol. They are present in numerous foodstuffs and have been demonstrated to be present at increased levels in the plasma of patients with cardiovascular diseases and in atherosclerotic lesions. Thus, their role in lipid disorders is widely suspected, and they might also be involved in important degenerative diseases such as Alzheimer's disease, osteoporosis, and age-related macular degeneration. Since atherosclerosis is associated with the presence of apoptotic cells and with oxidative and inflammatory processes, the ability of some oxysterols, especially 7-ketocholesterol and 7β-hydrox…
α-Tocopherol impairs 7-ketocholesterol-induced caspase-3-dependent apoptosis involving GSK-3 activation and Mcl-1 degradation on 158N murine oligoden…
2011
Abstract In important and severe neurodegenerative pathologies, 7-ketocholesterol, mainly resulting from cholesterol autoxidation, may contribute to dys- or demyelination processes. On various cell types, 7-ketocholesterol has often been shown to induce a complex mode of cell death by apoptosis associated with phospholipidosis. On 158N murine oligodendrocytes treated with 7-ketocholesterol (20 μg/mL corresponding to 50 μM, 24–48 h), the induction of a mode of cell death by apoptosis characterised by the occurrence of cells with condensed and/or fragmented nuclei, caspase activation (including caspase-3) and internucleosomal DNA fragmentation was observed. It was associated with a loss of tr…