Importance of cholesterol-phospholipid interaction in determining dynamics of normal and abetalipoproteinemia red blood cell membrane |
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Authors: | Yechezkel Barenholz Elishalom Yechiel Rivka Cohen Richard J Deckelbaum |
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Institution: | (1) Laboratory of Neurochemistry, Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel;(2) the Departments of Pediatrics and Gastroenterology, Hebrew University-Hadassah Medical School, Jerusalem, Israel;(3) the Department of Biochemistry, School of Medicine, University of Virginia, 22908 Charlottesville, VA, USA |
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Abstract: | Acanthocytic red blood cells in patients with abetalipoproteinemia have a decreased membrane fluidity that is associated with
increased sphingomyelin/phosphatidylcholine (SM/PC)§ ratios. Here we describe studies designed to gain better insight into
(i) the interrelationship between the composition of lipoprotein and red blood cell membrane in abetalipo-proteinemia patients
and normal controls; and (ii) how the differences in lipid composition of the red blood cell membrane affect its fluidity.
The increased SM/PC ratio found in abetalipoproteinemia plasma high density lipoproteins (HDL) (3 times greater than controls)
was paralleled by an increase in this ratio in acanthocytic red cells, but to a lesser degree (almost twice greater than control
red cells). Cholesterol/phospholipid mole ratios (C/P) were increased 3-fold in abetalipoproteinemia HDL, but only slightly
increased in red cells compared to controls values. As in the controls, 80–85% of abetalipo-proteinemia red cell sphingomyelin
was found to be in the outer half of the erythrocyte membrane.
Membrane fluidity was defined in terms of microviscosity ({ie116-1}) between 5 and 42°C by the fluorescent polarization of
1,6-diphenylhexatriene (DPH) present in erythrocyte ghost membranes. At all temperatures, membrane microviscosity was higher
in abetalipoproteinemia ghosts than controls, but these differences decreased at higher temperatures (12.34 vs 9.79 poise,
respectively, at 10°C; 4.63 vs 4.04 poise at 37°C). These differences were eliminated after oxidation of all membrane cholesterol
to cholest-4-en-3-one by incubation with cholesterol oxidase. Following cholesterol oxidation, the membrane microviscosity
decreased in patient ghosts more than in normal red blood cells so that at all temperatures no significant differences were
present relative to control ghosts, in which the apparent microviscosity was also diminished but to a lesser degree.
Therefore, although increased SM/PC ratios in abetalipoproteinemia may be responsible for decreased erythrocyte membrane fluidity,
these effects are dependent upon normal interactions of cholesterol with red cell phospholipid. |
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Keywords: | Cholesterol-phospholipid interaction in red blood cell membranes phospholipid-cholesterol interaction in red blood cell membranes red blood cell membranes cholesterol-phospholipid interaction in blood cell membranes lipoproteinemia in cell membranes lipoproteinemia in red blood membranes lipoproteinemia in red blood cell lipoproteinemia in red blood cell membranes abetalipoproteinemia in red blood cell membranes sphingomyelin-phosphatidyl-choline ratio |
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