We investigated the effects of glucose on specific D-α-tocopherol binding to cultured bovine aortic endothelial cells. Our results confirmed that cultured bovine aortic endothelial cells have specific binding sites for D-α-tocopherol. These binding sites exhibited time- and temperature-dependent saturation. The specific binding affinity of D-α-tocopherol was significantly lower in endothelial cells cultured in high concentrations of glucose (16.8 or 22.4 mM) for > 7 days compared with cells cultured in a physiological glucose concentration (5.6 mM). No significant reduction occurred in D-α-tocopherol binding when 11.1 mM mannitol was added to cells cultured in 5.6 mM glucose. The addition of an aldose reductase inhibitor (ICI-128436, Statil) did not significantly affect the high-glucose–induced reduction of D-α-tocopherol binding, although it reduced sorbitol levels in the cells compared with those from cells cultured in high concentrations of glucose. Moreover, significantly higher amounts of lipid peroxides were produced in aortic endothelial cells cultured in high concentrations of glucose (16.8 or 22.4 mM) for >3 days compared with cells cultured in a physiological concentration of glucose. These results indicate that high concentrations of glucose reduce D-α-tocopherol binding through mechanisms independent of putative osmotic effects of sorbitol accumulation in the cells. Possible mechanisms include glycation of protein or oxidative damage of cells and/or redox and metabolic imbalances associated with increased flux of glucose via the sorbitol pathway. A glucose-mediated reduction in D-α-tocopherol binding could diminish the beneficial effects of D-α-tocopherol to vascular endothelial cells and thereby may increase the vascular toxicity of hyperglycemia in diabetes mellitus.
High Glucose Reduces Specific Binding for D-α-Tocopherol in Cultured Aortic Endothelial Cells
Makoto Kunisaki, Fumio Umeda, Teruaki Yamauchi, Mitunori Masakado, Hajime Nawata; High Glucose Reduces Specific Binding for D-α-Tocopherol in Cultured Aortic Endothelial Cells. Diabetes 1 August 1993; 42 (8): 1138–1146. https://doi.org/10.2337/diab.42.8.1138
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