Advanced glycation end products induce specific glycoprotein alterations in retinal microvascular cells.
In order to investigate the mechanisms involved in diabetic retinopathy, 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 affinoblotting and metabolic radiolabeling with sugar precursors. Selective modifications in the glycoprotein sugar chains were observed mainly in BREC and for a 210 kDa membrane glycoprotein. Indeed, a 40% decrease of alpha(2,3) sialic acid, beta(1,3) galactose or alpha(1,6) fucose content was observed without significant protein amount changes. These glycoprotein alterations were related to the concentration of AGE. Neither BRP 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-translational modification, in this case glycation, could modify another post-translational process such as the enzymatic glycosylation.
Rellier
N
N
Diabetic Microangiopathy Research Unit, LIPHA-INSERM U352, INSA-Lyon, Villeurbanne, France.
Ruggiero
D
D
Lecomte
M
M
Lagarde
M
M
Wiernsperger
N
N
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000209:etiology; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D037102:Lectins / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology; D008833:Microcirculation; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D006023:Glycoproteins; D037102:Lectins; D009844:Oligosaccharides; D008353:Mannitol; D019158:N-Acetylneuraminic Acid; D005947:Glucose; D005690:Galactose