IDENTIFICATION OF THE MAJOR SITE OF APOLIPOPROTEIN-B MODIFICATION BY ADVANCED GLYCOSYLATION END-PRODUCTS BLOCKING UPTAKE BY THE LOW-DENSITY-LIPOPROTEIN RECEPTOR
R. Bucala et al., IDENTIFICATION OF THE MAJOR SITE OF APOLIPOPROTEIN-B MODIFICATION BY ADVANCED GLYCOSYLATION END-PRODUCTS BLOCKING UPTAKE BY THE LOW-DENSITY-LIPOPROTEIN RECEPTOR, The Journal of biological chemistry, 270(18), 1995, pp. 10828-10832
Advanced glycosylation end products (AGEs) arise from glucose-derived
Amadori products and have been implicated in the pathogenesis of diabe
tic vascular disease, We recently reported the presence of an AGE-modi
fied form of low density lipoprotein (LDL) that circulates in high amo
unts in patients with diabetes or renal insufficiency and that exhibit
s impaired plasma clearance kinetics, We utilized AGE-specific antibod
ies to identify the major sites of AGE modification within protease-di
gested preparations of apolipoprotein B that impair the binding of the
AGE-modified form of LDL by human fibroblast LDL receptors, The predo
minant site of AGE immunoreactivity was found to lie within a single,
67-amino acid region located 1791 residues NH2-terminal of the putativ
e LDL receptor binding domain, These data point to the high reactivity
and specificity of this site for AGE formation and provide further ev
idence for important structural interactions between the LDL receptor
binding domain and remote regions of the apolipoprotein B polypeptide.