Interaction of human low density lipoprotein and apolipoprotein B with ternary lipid microemulsion. Physical and functional properties |
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| Authors: | P W Chun E E Brumbaugh R B Shiremann |
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| Affiliation: | 1. División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México;2. Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México;3. Facultad de Medicina, Universidad Autónoma de Guadalajara, Guadalajara, Jalisco, México;1. Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE, SESANE, 92262, Fontenay-aux-Roses, France;2. Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional Departamento de Toxicología (CINVESTAV-IPN), Av. IPN No. 2508 Col., San Pedro Zacatenco, México City, CP 07360, Mexico;1. Department of Medical Biophysics, University of Toronto, Toronto, ON, M5G 1L7, Canada;2. Chemistry Department, York University, Toronto, ON, M3J 1P3, Canada;3. Centre for Research in Mass Spectrometry, York University, Toronto, ON, M3J 1P3, Canada;1. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia;2. Department of Genetics, Hamad Medical Corporation, Doha, Qatar;3. Department of Pediatrics, Security Forces Hospital, Riyadh 12625, Saudi Arabia;4. Department of Biostatistics, Epidemiology, and Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia;5. The Jackson Laboratory, Bar Harbor, ME 04609, USA;6. Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia;1. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada;3. Department of Medicine, McMaster University, Hamilton, Ontario, Canada;2. Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada |
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| Abstract: | Based on data from sedimentation velocity experiments, electrophoresis, electron microscopy, cellular uptake studies, scanning molecular sieve chromatography using a quasi-three-dimensional data display and flow performance liquid chromatography (FPLC), models for the interaction of human serum low density lipoprotein (LDL) and of apolipoprotein B (apo B) with a ternary lipid microemulsion (ME) are proposed. The initial step in the interaction of LDL (Stokes radius 110 A) with the ternary microemulsion (Stokes radius 270 A) appears to be attachment of the LDL to emulsion particles. This attachment is followed by a very slow fusion into particles having a radius of approx. 280 A. Sonication of this mixture yields large aggregates. Electron micrographs of deoxycholate-solubilized apo B indicate an arrangement of apo B resembling strings of beads. During incubation, these particles also attach to the ternary microemulsion particles and, upon sonication, spherical particles result which resemble native LDL particles in size. Scanning chromatography corroborates the electron microscopy results. By appropriate choice of display angles in a quasi-three-dimensional display of the scanning data (corrected for gel apparent absorbance) taken at equal time intervals during passage of a sample through the column, changes in molecular radius of less than 10 A can be detected visually. Such a display gives a quantitative estimate of 101 +/- 2 A for these particles (compared to 110 A for native LDL). The LDL-ME particles and apo B-ME particles compete efficiently with native LDL for cellular binding and uptake. Cellular association studies indicate that both LDL- and apo B-ME particles are effective vehicles for lipid delivery into cells. |
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