Search results for "cholesterol"

The superlattice model of lateral organization of membranes and its implications on membrane lipid homeostasis.

2008

AbstractMost biological membranes are extremely complex structures consisting of hundreds of different lipid and protein molecules. According to the famous fluid-mosaic model lipids and many proteins are free to diffuse very rapidly in the plane of the membrane. While such fast diffusion implies that different membrane lipids would be laterally randomly distributed, accumulating evidence indicates that in model and natural membranes the lipid components tend to adopt regular (superlattice-like) distributions. The superlattice model, put forward based on such evidence, is intriguing because it predicts that 1) there is a limited number of allowed compositions representing local minima in mem…

Evaluation of the cytotoxic effect of 7keto-stigmasterol and 7keto-cholesterol in human intestinal (Caco-2) cells

2012

The biological implications of cholesterol oxidation products have been investigated, though research on plant sterol oxidation products is scarce and in some cases contradictory. The cytotoxicity of 7keto(k)-stigmasterol versus 7keto(k)-cholesterol at different concentrations (0-120 μM) and incubation times (4-24h), in intestinal epithelial cells (Caco-2 cells) was evaluated. The 3-[4,5-dimethylthiazol-2-yl]-2,3-diphenyl tetrazolium bromide and neutral red uptake tests, mitochondrial membrane potential (ΔΨm), and relative DNA and RNA contents in the cell cycle phases were determined. Possible interaction effects between 7k-derivatives or non-oxidized stigmasterol were monitored. Endo/lysos…

Loss of γ-secretase function impairs endocytosis of lipoprotein particles and membrane cholesterol homeostasis

2008

Cholesterol-Like Effects of Selective Cyclooxygenase Inhibitors and Fibrates on Cellular Membranes and Amyloid-β Production

2007

Strong evidence suggests a mechanistic link between cholesterol metabolism and the formation of amyloid-beta peptides, the principal constituents of senile plaques found in the brains of patients with Alzheimer's disease. Here, we show that several fibrates and diaryl heterocycle cyclooxygenase inhibitors, among them the commonly used drugs fenofibrate and celecoxib, exhibit effects similar to those of cholesterol on cellular membranes and amyloid precursor protein (APP) processing. These drugs have the same effects on membrane rigidity as cholesterol, monitored here by an increase in fluorescence anisotropy. The effect of the drugs on cellular membranes was also reflected in the inhibitory…

Specific release of membrane-bound annexin II and cortical cytoskeletal elements by sequestration of membrane cholesterol

1997

Annexin II is an abundant protein which is present in the cytosol and on the cytoplasmic face of plasma membrane and early endosomes. It is generally believed that this association occurs via Ca(2+)-dependent binding to lipids, a mechanism typical for the annexin protein family. Although previous studies have shown that annexin II is involved in early endosome dynamics and organization, the precise biological role of the protein is unknown. In this study, we found that approximately 50% of the total cellular annexin was associated with membranes in a Ca(2+)-independent manner. This binding was extremely tight, since it resisted high salt and, to some extent, high pH treatments. We found, h…

DeepSRE: Identification of sterol responsive elements and nuclear transcription factors Y proximity in human DNA by Convolutional Neural Network anal…

2021

SREBP1 and 2, are cholesterol sensors able to modulate cholesterol-related gene expression responses. SREBPs binding sites are characterized by the presence of multiple target sequences as SRE, NFY and SP1, that can be arranged differently in different genes, so that it is not easy to identify the binding site on the basis of direct DNA sequence analysis. This paper presents a complete workflow based on a one-dimensional Convolutional Neural Network (CNN) model able to detect putative SREBPs binding sites irrespective of target elements arrangements. The strategy is based on the recognition of SRE linked (less than 250 bp) to NFY sequences according to chromosomal localization derived from …

Synthesis, Structural Elucidation, and Biological Evaluation of NSC12, an Orally Available Fibroblast Growth Factor (FGF) Ligand Trap for the Treatme…

2016

NSC12 is an orally available pan-FGF trap able to inhibit FGF2/FGFR interaction and endowed with promising antitumor activity. It was identified by virtual screening from a NCI small molecule library, but no data were available about its synthesis, stereochemistry, and physicochemical properties. We report here a synthetic route that allowed us to characterize and unambiguously identify the structure of the active compound by a combination of NMR spectroscopy and in silico conformational analysis. The synthetic protocol allowed us to sustain experiments aimed at assessing its therapeutic potential for the treatment of FGF-dependent lung cancers. A crucial step in the synthesis generated a c…

Effect of cholesterol on the physical properties of pulmonary surfactant films: Atomic force measurements study

2006

International audience; Atomic force measurements were performed on supported pulmonary surfactant (PS) films to address the effect of cholesterol on the physical properties of lung surfactant films. We recently found that cholesterol in excess of a physiological proportion abolishes surfactant function, and is the reason that surfactant fails to lower the surface tension upon compression. In this study, we investigated how the loss of mechanical stability observed earlier is related to the local mechanical properties of the film by local force measurements. The presence of 20% of cholesterol in bovine lipid extract surfactant (BLES) resulted in a decrease of the observed adhesive interacti…

Structure of Rhodococcus erythropolis limonene-1,2-epoxide hydrolase reveals a novel active site

2003

Epoxide hydrolases are essential for the processing of epoxide-containing compounds in detoxification or metabolism. The classic epoxide hydrolases have an alpha/beta hydrolase fold and act via a two-step reaction mechanism including an enzyme-substrate intermediate. We report here the structure of the limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis, solved using single-wavelength anomalous dispersion from a selenomethionine-substituted protein and refined at 1.2 A resolution. This enzyme represents a completely different structure and a novel one-step mechanism. The fold features a highly curved six-stranded mixed beta-sheet, with four alpha-helices packed onto it to create a …

Cholesterol oxidase: ultrahigh-resolution crystal structure and multipolar atom model-based analysis

2015

International audience; Author(s) of this paper may load this reprint on their own web site or institutional repository provided that this cover page is retained. Republication of this article or its storage in electronic databases other than as specified above is not permitted without prior permission in writing from the IUCr. For further information see http://journals.iucr.org/services/authorrights.html Acta Cryst. (2015). D71, 954-968 Zarychta et al. · Cholesterol oxidase research papers 954 http://dx. Examination of protein structure at the subatomic level is required to improve the understanding of enzymatic function. For this purpose, X-ray diffraction data have been collected at 100…