MOLECULAR IDENTITY AND CELLULAR-DISTRIBUTION OF ADVANCED GLYCATION ENDPRODUCT RECEPTORS - RELATIONSHIP OF P60 TO OST-48 AND P90 TO 80K-H MEMBRANE-PROTEINS

Advanced glycation endproducts (AGEs) are derivatives of nonenzymatic reactions between sugars and protein or lipids, and together with AGE- specific receptors are involved in numerous pathogenic processes assoc iated with aging and hyperglycemia. Two of the known AGE-binding prote ins isolated from rat liver membranes, p60 and p90, have been partiall y sequenced. We now report that the N-terminal sequence of p60 exhibit s 95% identity to OST-48, a 48-kDa member of the oligosaccharyltransfe rase complex found in microsomal membranes, while sequence analysis of p90 revealed 73% and 85% identity to the N-terminal and internal sequ ences, respectively, of human 80K-H, a 80- to 87-kDa protein substrate for protein kinase C. AGE-ligand and Western analyses of purified oli gosaccharyltransferase complex, enriched rough endoplasmic reticulum, smooth endoplasmic reticulum, and plasma membranes from rat liver or R AW 264.7 macrophages yielded a single protein of approximate to 50 kDa recognized by both anti-p60 and anti-OST-48 antibodies, and also exhi bited AGE-specific binding, Immunoprecipitated OST-48 from rat rough e ndoplasmic reticulum fractions exhibited both AGE binding and immunore activity to an anti-p60 antibody. Immune IgG raised to recombinant OST -48 and 80K-H inhibited binding of AGE-bovine serum albumin to cell me mbranes in a dose-dependent manner, Immunostaining and flow cytometry demonstrated the surface expression of OST-48 and 80K-H on numerous ce ll types and tissues, including mononuclear, endothelial, renal, and b rain neuronal and glial cells, We conclude that the AGE receptor compo nents p60 and p90 are identical to OST-48, and 80K-H, respectively, an d that they together contribute to the processing of AGEs from extra- and intracellular compartments and in the cellular responses associate d with these pathogenic substances.