The Effect of a-Tocopherol on Copper Binding to Low Density Lipoprotein

The oxidative modification of low density lipoprotein (ldl) may play an important rolein atherogenesis. antioxidants that can prevent ldl oxidation may act as antiatherogens. ourunderstanding ofthe mechanism ofldloxidation and factors that determine its susceptibility tooxidation is still incomplete. copper is a candidate for oxidizing ldl in atherosclerotic lesions.the binding of copper ions to ldl is usually thought to be a prerequisite for ldl oxidation bycopper. therefore we investigated the effect ofa-tocopherol (as a major fat soluble antioxidant)on copper bound to ldl and furthermore effect of this binding on the susceptibility ofldl tooxidative modification.in this study ldl was isolated from edta-plasma (1 mg edta/ml blood) byultracentrifugation using a single-step discontinuous gradient. then a-tocopherol was added toldl and incubated for i hat 37° c. the oxidation rate ofldl was estimated by thiobarbitoricacid reactive substances (tbars) after cus04 addition. finally, the effect of a-tocopherol onformation ofldl-copper complex by gel filtration was studied.our results showed that a-tocopherol (dose dependently) suppressed the formation oftbars and ldl-copper complex. the a-tocopherol with concentrations of 10, 50 and 100ilm reduced susceptibility of ldl to oxidative modification approximately by 2, 13 and 21percent, respectively. furthermore, addition of a-tocopherol to the ldl and cus04 mixturecontaining before hand prevented the formation of ldl-copper complex, approximately by30 percent.in conclusion we found that a-tocopherol with inhibition of copper binding to ldl maydecrease the susceptibility ofldl oxidation to this ion and thus could playa role in preventionofatherosclerosis.