Search results for "cholesterol"
showing 10 items of 1211 documents
Oxytocin receptors and cholesterol: interaction and regulation.
2000
Cholesterol affects the ligand binding function of the oxytocin receptor in a highly specific manner. While the structurally-related cholecystokinin receptor shows a strong correlation between the membrane fluidity and its binding function, the oxytocin receptor behaves differently. A stringent and unique requirement of the affinity state of the oxytocin receptor for structural features of the sterol molecule has been found. The molecular requirements differ both from those postulated for sterol-phospholipid interactions and from those known to be necessary for the activity of other proteins. Employing a new detergent-free subcellular fractionation protocol, a two-fold enrichment of the oxy…
Molecular modelling study of the role of cholesterol in the stimulation of the oxytocin receptor.
2001
Cholesterol, an integral component of membranes in Eucaryota, is a modifier of membrane properties. In vivo studies have demonstrated that cholesterol can also modulate activities of some G protein-coupled receptors (GPCRs), which are integral membrane proteins. This can result either from an effect of cholesterol on the membrane fluidity or from specific interactions of the membrane cholesterol with the receptor, as recently demonstrated for the cholecystokinin type beta (CCKRbeta) or the oxytocin receptor (OTR). Using molecular modelling, we studied conformational preferences of cholesterol and several of its analogues. Subsequently, we simulated the distributions of their preferred confo…
The 1.45 A resolution structure of the cryptogein-cholesterol complex: a close-up view of a sterol carrier protein (SCP) active site.
2002
Cryptogein is a small 10 kDa elicitor produced by the phytoparasitic oomycete Phytophthora cryptogea. The protein also displays a sterol carrier activity. The native protein crystallizes in space group P4(1)22, with unit-cell parameters a = b = 46.51, c = 134.9 A (diffraction limit: 2.1 A). Its complex with cholesterol crystallizes in space group C222(1), with unit-cell parameters a = 30.96, b = 94.8, c = 65.3 A and a resolution enhanced to 1.45 A. The large inner non-specific hydrophobic cavity is able to accommodate a large variety of 3-beta-hydroxy sterols. Cryptogein probably acts as a sterol shuttle helping the pathogen to grow and complete its life cycle.
Correlation of Pharmacological Properties of a Group of Hypolipaemic Drugs by Molecular Topology
1996
Abstract This investigation was undertaken to test the ability of the molecular connectivity model to predict the percentage of plasma protein binding, the percentage of total cholesterol reduction and oral LD50 in rats of a group of hypolipaemic drugs using multi-variable regression equations with multiple correlation coefficients, standard error of estimate, degrees of freedom, F-Snedecor function values, Mallow's CP and Student's t-test as criteria of fit. Regression analyses showed that the molecular connectivity model predicts these properties. Corresponding stability (cross validation) studies were made on the selected prediction models which confirmed their goodness of fit. The resul…
Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patien…
2015
OBJECTIVE: To compare lipid-lowering efficacy of adding alirocumab to rosuvastatin versus other treatment strategies (NCT01730053).METHODS: Patients receiving baseline rosuvastatin regimens (10 or 20 mg) were randomized to: add-on alirocumab 75 mg every-2-weeks (Q2W) (1-mL subcutaneous injection via pre-filled pen); add-on ezetimibe 10 mg/day; or double-dose rosuvastatin. Patients had cardiovascular disease (CVD) and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (1.8 mmol/L) or CVD risk factors and LDL-C ≥100 mg/dL (2.6 mmol/L). In the alirocumab group, dose was blindly increased at Week 12 to 150 mg Q2W (also 1-mL volume) in patients not achieving their LDL-C target. Primary endpoi…
The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management.
2014
Item does not contain fulltext Plasma triglyceride concentration is a biomarker for circulating triglyceride-rich lipoproteins and their metabolic remnants. Common mild-to-moderate hypertriglyceridaemia is typically multigenic, and results from the cumulative burden of common and rare variants in more than 30 genes, as quantified by genetic risk scores. Rare autosomal recessive monogenic hypertriglyceridaemia can result from large-effect mutations in six different genes. Hypertriglyceridaemia is exacerbated by non-genetic factors. On the basis of recent genetic data, we redefine the disorder into two states: severe (triglyceride concentration >10 mmol/L), which is more likely to have a mono…
Regulation of cholesterol metabolism in the retina under experimental conditions associated with glaucoma
2019
Cholesterol is a lipid found in every animal cell and is necessary for its survival. Among its multiple roles in the body, it is a component of cell membranes that is crucial for the maintenance of their structure and fluidity and is thus implicated in the modulation of many signalling pathways. Neurons are especially dependant on cholesterol input since the proper composition of their plasma membrane is required for vesicular exocytosis of neurotransmitters and transduction of the post-synaptic signal. It has been shown that both an excess and a lack of cholesterol is neurotoxic. Moreover, many neurodegenerative diseases, such as Alzheimer’s or Huntington’s disease, have been associated wi…
Phytochemical indicaxanthin suppresses 7-ketocholesterol-induced THP-1 cell apoptosis by preventing cytosolic Ca++ increase and oxidative stress
2013
7-Ketocholesterol (7-KC)-induced apoptosis of macrophages is considered a key event in the development of human atheromas. In the present study, the effect of indicaxanthin (Ind), a bioactive pigment from cactus pear fruit, on 7-KC-induced apoptosis of human monocyte/macrophage THP-1 cells was investigated. A pathophysiological condition was simulated by using amounts of 7-KC that can be reached in human atheromatous plaque. Ind was assayed within a micromolar concentration range, consistent with its plasma level after dietary supplementation with cactus pear fruit. Pro-apoptotic effects of 7-KC were assessed by cell cycle arrest, exposure of phosphatidylserine at the plasma membrane, varia…
Protective effect of antioxidants contained in milk-based fruit beverages against sterol oxidation products
2017
Abstract Sterol oxidation products (SOPs) have shown cytotoxic effect in human intestinal cells; however, their effect within a food matrix has not been assayed yet. This study evaluated the possible cytotoxic effect of SOPs within bioaccessible fractions (BFs) of two milk-based fruit beverages with (BFA)/without (BFB) plant sterols in differentiated Caco-2 cells and if the BFs counteracted the cytotoxic effect induced by COPs mixture (30 and 60 μM). BFs did not evoke cytotoxic effect in any of the tests carried out and they protected against the loss of intestinal cohesion, mitochondrial depolarization and necrosis induced by COPs mixture. Moreover, BFB sample protected from cell cycle arr…
Short-term atorvastatin treatment does not modify neointimal morphology but reduces MMP-2 expression in normocholesterolemic rabbit stented arteries.
2006
The aim of our study was to explore some potential pleiotropic effects of atorvastatin, after stenting in the iliac arteries of normocholesterolemic rabbits. On day 0, 27 rabbits underwent stent implantation and were randomized into either the control group (standard chow, CTRL, n = 15) or the atorvastatin group (10 mg/kg/d per os, Ator, n = 12). On day 30, the stented arteries were harvested for histomorphometry and neointimal analysis [macrophages, matrix metalloproteinases (MMP-2), tissue inhibitor of metalloproteinase-2, vascular smooth muscle cells, and collagen]. Atorvastatin did not induce significant histomorphometric and inflammatory modifications but reduced neointimal expression …