title: Identification of the major site of apolipoprotein B modification by advanced glycosylation end products blocking uptake by the low density lipoprotein receptor.
abstract: Advanced glycosylation end products (AGEs) arise from glucose-derived Amadori products and have been implicated in the pathogenesis of diabetic vascular disease. We recently reported the presence of an AGE-modified form of low density lipoprotein (LDL) that circulates in high amounts in patients with diabetes or renal insufficiency and that exhibits impaired plasma clearance kinetics. We utilized AGE-specific antibodies to identify the major sites of AGE modification within protease-digested preparations of apolipoprotein B that impair the binding of the AGE-modified form of LDL by human fibroblast LDL receptors. The predominant site of AGE immunoreactivity was found to lie within a single, 67-amino acid region located 1791 residues NH2-terminal of the putative LDL receptor binding domain. These data point to the high reactivity and specificity of this site for AGE formation and provide further evidence for important structural interactions between the LDL receptor binding domain and remote regions of the apolipoprotein B polypeptide.
authors.affiliation: Picower Institute for Medical Research, Manhasset, New York 11030, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bucala
authors.forename: R
authors.initials: R
authors.lastname: Mitchell
authors.forename: K
authors.initials: K
authors.lastname: Arnold
authors.forename: T
authors.initials: T
authors.lastname: Innerarity
authors.forename: H
authors.initials: H
authors.lastname: Vlassara
authors.forename: A
authors.initials: A
authors.lastname: Cerami
mesh_terms: D000595:Amino Acid Sequence; D001055:Apolipoproteins B / Q000737:chemistry* / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D011973:Receptors, LDL / Q000378:metabolism*
chemical_list: D001055:Apolipoproteins B; D017127:Glycation End Products, Advanced; D011973:Receptors, LDL