ADVANCED GLYCATION END-PRODUCTS INDUCE SPECIFIC GLYCOPROTEIN ALTERATIONS IN RETINAL MICROVASCULAR CELLS

In order to investigate the mechanisms involved in diabetic retinopath y, we studied the effects of advanced glycosylation end products (AGE) on retinal microvascular cell glycoproteins, Bovine retinal pericytes (BRP) and endothelial cells (BREC) were incubated in the presence of AGE-modified albumin and cell glycoproteins analyzed by lectin affinob lotting and metabolic radiolabeling with sugar precursors. Selective m odifications in the glycoprotein sugar chains were observed mainly in BREC and for a 210 kDa membrane glycoprotein. Indeed, a 40% decrease o f alpha(2,3) sialic acid, beta(1,3) galactose or alpha(1,6) fucose con tent was observed without significant protein amount changes. These gl ycoprotein alterations were related to the concentration of AGE. Neith er ERP nor BREC glycoproteins were modified when cells were incubated with high glucose or fructose concentrations. These results suggest a new diabetic pathogenic mechanism in which a protein post-translationa l modification, in this case glycation, could modify another post-tran slational process such as the enzymatic glycosylation. (C) 1997 Academ ic Press.