Glucose Influence on Copper Ion-Dependent Oxidation of Low Density Lipoprotein

Background: It is well established that oxidative modification of low density lipoprotein (LDL) plays a causal role in human atherogenesis and the risk of atherosclerosis is increased in patients with diabetes mellitus. We examined the in vitro effect of glucose on native and glycated LDL oxidation using copper ion dependent oxidation system. Methods: In this study, LDL was isolated from plasma by ultracentrifugation using a single step discontinuous gradient. Native LDL preparations were glycated by glucose and also were oxidized by copper ions. LDL glycation and oxidation levels were estimated by sodium periodate assay and thiobarbituric acid reactive substances (TBARS), respectively. Then, native LDL was incubated with glucose and copper and LDL oxidation was estimated by TBARS. Finally, oxidation of glycated LDL was studied in presence of copper ions by TBARS and relative electrophoretic mobility on polyacrylamide gel. Results: This study showed that glucose considerably decreased the oxidation of native LDL by copper ions. But oxidation of glycated LDL elevated with presence of copper ions. Conclusion: The results of this investigation show that LDL glycated in vitro is prone to oxidation by copper ions. Thus, promotion of glycated LDL oxidation by glucose is specific for copper ion dependent oxidation and involves increased copper ion reduction. These results provide one mechanism that may enhanced LDL oxidation in diabetes and thus contribute to the pathogenesis of atherosclerosis in diabetic patients.