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  • Title: Characterization of the advanced glycation end-product receptor complex in human vascular endothelial cells.
    Author: Stitt AW, He C, Vlassara H.
    Journal: Biochem Biophys Res Commun; 1999 Mar 24; 256(3):549-56. PubMed ID: 10080935.
    Abstract:
    Advanced glycation end products (AGEs) have been implicated as causal factors in the vascular complications of diabetes and it is known that these products interact with cells through specific receptors. The AGE-receptor complex, originally described as p60 and p90, has been characterised in hemopoietic cells and the component proteins identified and designated AGE-R1, -R2 and -R3. In the current study we have characterised this receptor in human umbilical vein endothelial cells (HUVECs) and elucidated several important biological properties which may impact on AGE mediated vascular disease. 125I-AGE-BSA binding to HUVEC monolayers was determined with and without various cold competitors. The synthetic AGE, 2-(2-furoyl)-4(5)-furanyl-1H-imidazole (FFI)-BSA, failed to compete with AGE-BSA binding unlike observations already reported in hemopoietic cells. The ability of 125I-AGE-BSA to bind to separated HUVEC plasma membrane (PM) proteins was also examined and the binding at specific bands inhibited by antibodies to each component of the AGE-receptor complex. Western blotting of whole cell and PM fractions, before and after exposure to AGE-BSA, revealed that AGE-R1, -R2 and -R3 are subject to upregulation upon exposure to their ligand, a phenomenon which was also demonstrated by immunofluorescence of non-permeabilised cells. mRNA expression of each AGE-receptor component was apparent in HUVECs, with the AGE-R2 and -R3 gene expression being upregulated upon exposure to AGEs in a time-dependent manner. A phosporylation assay in combination with AGE-R2 immunoprecipitation demonstrated that this component of the receptor complex is phosphorylated by acute exposure to AGE-BSA. These results indicate the presence of a conserved AGE-receptor complex in vascular endothelium which demonstrates subtle differences to other cell-types. In response to AGE-modified molecules, this complex is subject to upregulation, while the AGE-R2 component also displays increased phosphorylation possibly leading to enhanced signal transduction.
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