Search results for "Hydroxycholesterols"
showing 10 items of 19 documents
EBI2 – Sensor for dihydroxycholesterol gradients in neuroinflammation
2018
Dihydroxycholesterols such as 7α,25-dihydroxysterols (7α,25-OHC) and 7α,27-OHC are generated from cholesterol by the enzymes CH25H, CYP7B1 and CYP27A1 in steady state but also in the context of inflammation. The G-protein coupled receptor (GPCR) Epstein-Barr virus-induced gene 2 (EBI2), also known as GPR183, senses these oxysterols and induces chemotactic migration of immune cells towards higher concentrations of these ligands. We recently showed that these ligands are upregulated in the CNS in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis and that EBI2 enhanced early infiltration of encephalitogenic T cells into the CNS. In this short-review we dis…
Attenuation of 7-ketocholesterol- and 7β-hydroxycholesterol-induced oxiapoptophagy by nutrients, synthetic molecules and oils: Potential for the prev…
2021
Age-related diseases for which there are no effective treatments include cardiovascular diseases; neurodegenerative diseases such as Alzheimer's disease; eye disorders such as cataract and age-related macular degeneration; and, more recently, Severe Acute Respiratory Syndrome (SARS-CoV-2). These diseases are associated with plasma and/or tissue increases in cholesterol derivatives mainly formed by auto-oxidation: 7-ketocholesterol, also known as 7-oxo-cholesterol, and 7β-hydroxycholesterol. The formation of these oxysterols can be considered as a consequence of mitochondrial and peroxisomal dysfunction, leading to increased in oxidative stress, which is accentuated with age. 7-ketocholester…
7-ketocholesterol and 7β-hydroxycholesterol: in vitro and animal models used to characterize their activities and to identify molecules preventing th…
2020
International audience; Oxysterols are molecules derived by the oxidation of cholesterol and can be formed either by auto-oxidation, enzymatically or by both processes. Among the oxysterols formed by auto-oxidation, 7-ketocholesterol and 7beta-hydroxycholesterol are the main forms generated. These oxysterols, formed endogenously and brought in large quantities by certain foods, have major cytotoxic properties. They are powerful inducers of oxidative stress, inducing dysfunction of organelles (mitochondria, lysosomes and peroxisomes) that can cause cell death. These molecules are often identified in increased amounts in common pathological states such as cardiovascular diseases, certain eye …
Inverse correlation between plasma oxysterol and LDL-cholesterol levels in hepatitis C virus-infected patients
2012
Background: Hepatitis C virus infection is characterised by enhanced oxidative stress, which can be measured quantitatively by plasma oxysterol concentration. These molecules may affect lipid metabolism through the activation of Liver X Receptors. Hepatitis C virus exploits host lipid metabolism to facilitate its replication and diffusion. In our study we aimed to evaluate and highlight the potential pathogenetic role of oxysterols, 7-ketocholesterol and 7-β-hydroxycholesterol, in hepatitis C virus-related lipid dysmetabolism. Methods: The study was performed in 42 patients with chronic hepatitis C (93% genotype 1b) and 38 non-alcoholic fatty liver disease patients. Plasma oxysterols 7-keto…
LXR antagonists induce ABCD2 expression
2014
X-linked adrenoleukodystrophy (X-ALD) is a rare neurodegenerative disorder characterized by the accumulation of very-long-chain fatty acids resulting from a beta-oxidation defect. Oxidative stress and inflammation are also key components of the pathogenesis. X-ALD is caused by mutations in the ABCDI gene, which encodes for a peroxisomal half ABC transporter predicted to participate in the entry of VLCFA-CoA into the peroxisome, the unique site of their beta-oxidation. Two homologous peroxisomal ABC transporters, ABCD2 and ABCD3 have been proven to compensate for ABCD1 deficiency when overexpressed. Pharmacological induction of these target genes could therefore represent an alternative ther…
Improved synthesis and in vitro evaluation of the cytotoxic profile of oxysterols oxidized at C4 (4α- and 4β-hydroxycholesterol) and C7 (7-ketocholes…
2013
Whereas the biological activities of oxysterols oxidized at C7 (7-ketocholesterol (7KC), 7β-hydroxycholesterol (7β-OHC), 7α-hydroxycholesterol (7α-OHC)) are well documented, those of oxysterols oxidized at C4 (4β-hydroxycholesterol (4β-OHC), 4α-hydroxycholesterol (4α-OHC)) are not well known, especially on the cells of the central nervous system. Therefore, an improved methodology has been validated for 4β-OHC and 4α-OHC synthesis, and the effects on cell viability and cell growth of these molecules were studied on immortalized, tumoral and normal brain cells (158N, C6 and SK-N-BE cells, and mixed primary cultures of astrocytes and oligodendrocytes). Whereas inhibition of cell growth with 7…
Impaired cellular cholesterol efflux by oxysterol-enriched high density lipoproteins.
1997
One of the proposed antiatherogenicity role of high-density lipoproteins (HDL) is believed to stimulate removal of cholesterol from the peripheral cells back to the liver for excretion. We have investigated the effects of oxidation-related modifications of HDL on their ability to stimulate cholesterol efflux from cultured cells. Human HDL (HDL3, 1.13 < d < 1.21 g/ml) have been modified either by malondialdehyde or by copper-mediated oxidation (Ox-HDL3). Compared with native HDL3, the modified HDL3 resulted in a significantly reduced efflux of labeled cholesterol from preloaded macrophages (P388D1 cell line). Analysis of lipid composition of Ox-HDL3 by gas chromatography revealed the presenc…
Activation of a caspase-3-independent mode of cell death associated with lysosomal destabilization in cultured human retinal pigment epithelial cells…
2008
International audience; Purpose: To characterize the possible cytotoxic effects of oxysterols (7-hydroxycholesterol (7-OH), 25-hydroxycholesterol (25-OH)) in human retinal pigment epithelial cells (ARPE-19) and to detail the relationships between some of these effects. Methods: ARPE-19 cells were treated with 7-OH and 25-OH. Cell viability was measured with the MTT assay. Membrane permeability, mitochondrial potential, and lysosomal integrity were measured by flow cytometry with propidium iodide, DiOC6(3), and acridine orange, respectively. Cell death was characterized by staining with Hoechst 33342, transmission electron microscopy, and analysis of the DNA fragmentation pattern. Caspase ac…
Steady-state levels of retinal 24S-hydroxycholesterol are maintained by glial cells intervention after elevation of intraocular pressure in the rat
2012
Purpose: Our previous studies suggested that CYP46A1 and 24S-hydroxycholesterol. (24SOH) may be associated with glaucoma. Loss of CYP46A1-expressing retinal. ganglion cells is involved in the activation of glia, and therefore possibly in the. disbalance of cholesterol. In this context, the purpose of our present work was to. emphasize the glial and longitudinal CYP46A1 expression after an interventional. glaucoma-related stress triggered by elevated intraocular pressure (IOP). Methods: Sprague–Dawley rats were submitted to laser photocoagulation of the. trabecular meshwork, limbus and episcleral veins in one eye to induce elevated IOP. Rats were euthanized at days 3, 14, 30 and 60 (n = 10 p…