Membrane interactions of a phosphomonoester elevated early in Alzheimer's disease
| Autor: | Jay W. Pettegrew, Mark W. Trumbore, R. Preston Mason |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Aging
food.ingredient Lipid Bilayers Biophysics Phospholipid Lecithin Biophysical Phenomena Phosphoserine chemistry.chemical_compound food X-Ray Diffraction Alzheimer Disease Phosphatidylcholine Humans Lipid bilayer phase behavior Lipid bilayer Liposome Calorimetry Differential Scanning Cholesterol General Neuroscience Bilayer technology industry and agriculture chemistry Biochemistry Liposomes lipids (amino acids peptides and proteins) Neurology (clinical) Geriatrics and Gerontology Dimyristoylphosphatidylcholine Developmental Biology |
| Zdroj: | Neurobiology of Aging. 16:531-539 |
| ISSN: | 0197-4580 |
| Popis: | Phosphoserine (L-PS) is among several phosphomonoesters found to be elevated in autopsied Alzheimer's disease (AD) brain tissue. To investigate the molecular interactions of L-PS with membrane lipid bilayers, small angle X-ray diffraction and high resolution differential scanning calorimetry (DSC) approaches were used with liposomes composed of lecithin and cholesterol. A one-dimensional electron density profile of a control dimyristoyl phosphatidylcholine (DMPC)/cholesterol lipid bilayer with a unit cell dimension of 52 A at 37 degrees C was generated from the X-ray diffraction data. Following incubation with 2.0 mM L-PS, a broad decrease in electron density +/- 4-12 A from the lipid bilayer center was observed concomitant with an increase in the width of the phospholipid headgroup electron density and a 3 A reduction in lipid bilayer width. The interactions of L-PS with DMPC lipid bilayers were concentration-dependent, highly affected by cholesterol content and reproduced in egg phosphatidylcholine/cholesterol liposomes. DSC analysis showed that millimolar (1.0-5.0 mM) L-PS levels decrease the phase transition cooperative unit size of DMPC liposomes in a highly concentration-dependent manner which was significantly greater in preparations containing cholesterol. The endotherm width at half-maximum doubled at 5.0 mM and 1.25 mM L-PS, respectively, for DMPC and DMPC/cholesterol liposomes. These data provide direct evidence that elevated phosphomonoester levels modulate the biophysical properties of the membrane lipid bilayer which may, in turn, lead to altered structure/function relationships in membranes during AD. |
| Databáze: | OpenAIRE |
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