Changes in erythrocyte membrane lipid composition affect the transient decrease in membrane order which accompanies insulin receptor down-regulation |
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Authors: | M T Santini R Masella A Cantafora S W Peterson |
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Institution: | (1) Laboratorio di Ultrastrutture and INFN-Sezione Sanità, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, (Italy);(2) Laboratorio di Metabolismo e Biochimica Patologica, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, (Italy);(3) Department of Biology, Arkansas College, 2300 Highland Road, 72501 Batesville, Arkansas, USA |
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Abstract: | We have recently demonstrated, using electron paramagnetic resonance (EPR) spectroscopy, that insulin receptor internalization in response to insulin incubation (down-regulation) in human erythrocytes is accompanied by a transient decrease in membrane order, as measured by the 2T![prime](/content/l818296592522026/xxlarge8242.gif) order parameter. Since membrane lipids play such an important role in receptor internalization, we investigated the possible effects that an alteration of the normally-occurring lipid profile might have on down-regulation and the concomitant transient decrease in membrane order. Consequently, human erythrocytes enriched with cholesterol and erythrocytes from cirrhotic patients were examined, because both of these groups of cells have a higher cholesterol/phospholipid molar ratio (CH/PL) than controls. The 5-nitroxystearate spin label, which inserts into the lipid bilayer of cell membranes, was used to monitor changes in 2T![prime](/content/l818296592522026/xxlarge8242.gif) for a 3-h period at 37°C. We report here that both cholesterol-enriched and cirrhotic erythrocytes do not down-regulate, as demonstrated by binding assays, and that they do not show the typical transient decrease in membrane order observed in controls. The results seem to indicate that a more ordered membrane inhibits internalization of the insulin receptor in erythrocytes, and that an increase in membrane disorder is necessary for insulin receptor down-regulation. |
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Keywords: | Erythrocyte insulin receptor receptor endocytosis EPR membrane order membrane lipids |
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