Lipid advanced glycosylation: pathway for lipid oxidation in vivo.

• DOI: 10.1073/pnas.90.14.6434
• Publication Date: 2006-05-31T12:27:18Z
• Authors: R Bucala; Z Makita; T Koschinsky; A Cerami; H Vlassara
• Keywords: Lipid Oxidation; Advanced glycation end-product

To address potential mechanisms for oxidative modification of lipids in vivo, we investigated the possibility that phospholipids react directly with glucose to form advanced glycosylation end products (AGEs) then initiate lipid oxidation. Phospholipid-linked AGEs formed readily vitro, mimicking absorbance, fluorescence, and immunochemical properties result from proteins. Oxidation unsaturated fatty acid residues, as assessed by reactive aldehyde formation, occurred at a rate paralleled glycosylation. Aminoguanidine, an agent prevents protein glycosylation, inhibited both modification. Incubation low density lipoprotein (LDL) produced AGE moieties were attached apoprotein components. Oxidized LDL concomitantly AGE-modified LDL. Of significance, ELISA analysis specimens isolated diabetic individuals revealed increased levels apoprotein- lipid-linked when compared obtained normal, nondiabetic controls. Circulating oxidized elevated patients correlated significantly levels. These data support concept oxidation plays important perhaps primary role initiating vivo.