14 research outputs found

    Effect of cationic lipids in the formation of asymmetries in supported bilayers.

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    We have studied the formation of a supported bilayer containing both cationic and zwitterionic lipids by fusion of small unilamellar vesicles (SUV) onto the solid surface at low salt conditions using a combination of attenuated total reflection infrared (ATR-IR) and deuterium NMR spectroscopy with microcalorimetry. The data suggest that a significant cationic lipid asymmetry between the outer (distal) and the inner (proximal) monolayer of a supported bilayer results under conditions of prolonged incubation times of the solid support with the SUV coating solution. For a SUV composition of DPPC/DHDAB (4:1) we observed an enrichment of the cationic component in the proximal monolayer of up to 200% compared to the distal monolayer after 12 h incubation. It is suggested that the electrostatic potential arising from the solid surface is the driving force for the creation of this asymmetry by means of directed flip-flop between the monolayers and/or by temporary fusion between SUV from the bulk with the supported bilayer

    Increased activity of mitochondrial aldehyde dehydrogenase (ALDH) in the putamen of individuals with Alzheimer's disease: a human postmortem study

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    For decades, it has been acknowledged that oxidative stress due to free radical species contributes to the pathophysiology of aging and neurodegenerative diseases. Aldehyde dehydrogenases (ALDH) not only transform aldehydes to acids but also act as antioxidant enzymes. However, little is known about the implications of the enzymatic family of ALDH in the context of neurodegenerative processes such as Alzheimer's disease (AD). We therefore examined the enzymatic activity of the mitochondrial ALDH-isoform in different regions of the postmortem brain tissue isolated from patients with AD and controls. We found that the mitochondrial ALDH activity was significantly increased only in the putamen of patients suffering from AD compared to controls. This is of particular interest since mediators of oxidative stress, such as iron, are increased in the putamen of patients with AD. This study adds to the body of evidence that suggests that oxidative stress as well as aldehyde toxicity play a role in AD

    Lipid Nature and Their Influence on Opening of Redox-Active Liposomes

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    The pathway for contents release from reduction-sensitive liposomes based on a quinone-dioleoylphosphatidylethanolamine lipid conjugate (Q-DOPE) was outlined using results from fluorescent dye contents release assays, as well as single- and multiple-angle light scattering. Experimental observations are consistent with a shape/size change of the reduced liposomes prior to their aggregation, with subsequent near-quantitative contents release achieved only when the lipid membrane experiences conditions favorable to a lamellar to an inverted hexagonal phase transition. Addition of poly(ethyleneglycol)-modified DOPE (PEG-DOPE) to the Q-DOPE liposomal formulation results in stabilization of the lipid bilayer, whereas incorporation of DOPE yields faster contents release. At high DOPE concentrations, DOPE/PEG-DOPE/Q-DOPE liposomes exhibit larger contents release, indicating a change in pathway for contents release. The outcomes here provide a better understanding of the underlying principles of triggered liposomal contents release and the potential utility of specific lipid properties for the rational design of drug delivery systems based on the novel Q-DOPE lipid
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