Brain membrane cholesterol domains, aging and amyloid beta-peptides.

Lipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. These domains consist of the exofacial and cytofacial leaflets, cholesterol pools, annular lipids, and lipid rafts.

Amyloid beta-peptide1-40 increases neuronal membrane fluidity: role of cholesterol and brain region.

There is increasing evidence of an interaction between cholesterol dynamics and Alzheimer's disease (AD), and amyloid beta-peptide may play an important role in this interaction. Abeta destabilizes brain membranes and this action of Abeta may be dependent on the amount of membrane cholesterol. We tested this hypothesis by examining effects of Abeta1-40 on the annular fluidity (i.

Lipid carrier proteins and ethanol.

Ethanol has a pronounced effect on lipid homeostasis. It is our overall hypothesis that certain lipid carrier proteins are targets of acute and chronic ethanol exposure and that perturbation of these proteins induces lipid dysfunction leading to cellular pathophysiology. These proteins include both intracellular proteins and lipoproteins.

Cholesterol efflux to high-density lipoproteins and apolipoprotein A-I phosphatidylcholine complexes is inhibited by ethanol: role of apolipoprotein structure and cooperative interaction of phosphatidylcholine and cholesterol.

There is a substantial body of evidence showing that moderate alcohol consumption is associated with a reduced risk of cardiovascular morbidity and mortality. One of the factors thought to contribute to this reduction in risk is an increase in the level of high-density lipoproteins (HDL) correlated with alcohol consumption. However, HDL levels are elevated in heavy drinkers, but their risk of vascular disease is greater compared with that of moderate drinkers.

Distribution and fluidizing action of soluble and aggregated amyloid beta-peptide in rat synaptic plasma membranes.

The effects of soluble and aggregated amyloid beta-peptide (Abeta) on cortical synaptic plasma membrane (SPM) structure were examined using small angle x-ray diffraction and fluorescence spectroscopy approaches. Electron density profiles generated from the x-ray diffraction data demonstrated that soluble and aggregated Abeta1-40 peptides associated with distinct regions of the SPM. The width of the SPM samples, including surface hydration, was 84 A at 10 degrees C.

Recent advances in brain cholesterol dynamics: transport, domains, and Alzheimer's disease.

Major advances in understanding cholesterol dynamics and the role that cholesterol plays in vascular disease have recently been made. The brain is an organ that is highly enriched in cholesterol, but progress toward understanding brain cholesterol dynamics has been relatively limited. This review examines recent contributions to the understanding of brain cholesterol dynamics, focusing on extracellular and intracellular lipid carrier proteins, membrane cholesterol domains, and emerging evidence linking an association between cholesterol dynamics and Alzheimer's disease.

Lipid binding to sterol carrier protein-2 is inhibited by ethanol.

Sterol carrier protein-2 (SCP-2) is an intracellular lipid carrier protein that binds cholesterol, phospholipids, fatty acids and other ligands. It has been reported that expression of SCP-2 was increased in brain nerve endings or synaptosomes of chronic ethanol-treated mice and it was shown that cholesterol homeostasis was altered in brain membranes of chronic ethanol-treated animals. Ethanol may interfere with the capacity of SCP-2 to bind cholesterol as well as other lipids.

Lipid binding to amyloid beta-peptide aggregates: preferential binding of cholesterol as compared with phosphatidylcholine and fatty acids.

Amyloid beta-peptide (A beta) aggregates are one of the key neuropathological characteristics of Alzheimer's disease. A beta belongs to a group of proteins that aggregate and form beta-sheets, and some of these proteins bind cholesterol and other lipids. The purpose of the experiments reported here was to determine if cholesterol, fatty acids, and phosphatidylcholine (PC) would bind to A beta(1-40) and if such binding would be dependent on aggregation of A beta(1-40).

Transbilayer distribution of cholesterol is modified in brain synaptic plasma membranes of knockout mice deficient in the low-density lipoprotein receptor, apolipoprotein E, or both proteins.

Both apolipoprotein E (apoE) and the low-density lipoprotein (LDL) receptor are present in brain; however, little is known regarding the function of these proteins in brain, in particular with respect to brain cholesterol. The role of apoE and the LDL receptor in modulating the transbilayer or asymmetric distribution of cholesterol in the exofacial and cytofacial leaflets of synaptic plasma membranes (SPMs) was examined in mutant mice deficient in apoE, the LDL receptor, or both proteins by using the fluorescent sterol dehydroergosterol and fluorescent quenching procedures. Fluidity of the exofacial and cytofacial leaflets was also measured.

Amyloid beta-peptides increase annular and bulk fluidity and induce lipid peroxidation in brain synaptic plasma membranes.

Amyloid beta-peptides (A beta) may alter the neuronal membrane lipid environment by changing fluidity and inducing free radical lipid peroxidation. The effects of A beta(1-40) and A beta(25-35) on the fluidity of lipids adjacent to proteins (annular fluidity), bulk lipid fluidity, and lipid peroxidation were determined in rat synaptic plasma membranes (SPM). A fluorescent method based on radiationless energy transfer from tryptophan of SPM proteins to pyrene and pyrene monomer-eximer formation was used to determine SPM annular fluidity and bulk fluidity, respectively.

Direct binding of ethanol to bovine serum albumin: a fluorescent and 13C NMR multiplet relaxation study.

Molecular mechanisms of ethanol interaction with proteins are not well-understood. In the present study, direct interaction of ethanol with hydrophobic binding sites on fatty acid free bovine serum albumin (BSA) was determined using the fluorescent probe 1-anilinonaphthalene-8-sulfonic acid (1,8-ANS), cis-parinaric acid, and 13C NMR. The affinity of ethanol for BSA (Kd) was (5.

Chronic ethanol consumption alters effects of ethanol in vitro on brain membrane structure of high alcohol sensitivity and low alcohol sensitivity rats.

In this study, we examined if differences in initial membrane sensitivity to ethanol were associated with development of membrane tolerance to ethanol. High Alcohol Sensitivity (HAS) and Low Alcohol Sensitivity (LAS) rats were administered a 15% ethanol solution in water as the sole source of fluid for 30 days. The amount of ethanol consumed per day did not significantly differ between the HAS and LAS rats.