抄録
When serum low-density lipoprotein (LDL) was peroxidized and incubated with an epinephrine-FeCl3 mixture in the presence of spin trap 5, 5-dimethyl-l-pyrrolin-N-oxide (DMPO), an electron spin resonance spectrum indicative of the spin adduct of DMPO and hydroxyl radical (·OH) was detected. The amount of ·OH increased with an increase in the content of lipid hydroperoxides in the LDL. These results indicate that ·OH was generated from lipid hydroperoxides in the LDL and that cytotoxicity of peroxidized LDL is at least partly attributable to the hazardous effect of the ·OH thus generated. Since lipid hydroperoxides are rather stable and can be transferred from one site to another via LDL, we consider that lipid hydroperoxides are a propagator of radical-mediated injury to tissues and organs.
Serum LDL comprises distinct subclasses. We purified these three subfrations of LDL, LDL-1, LDL-2, and LDL-3, to homogeneity from hyper-cholesterolemic rabbits. On the basis of size and density distribution, LDL-1 corresponded to intermediate density lipoprotein obtained by the standard sequential floatation method. When the LDL subfractions were incubated in the presence of Cu2+, the lipid peroxide level and the mobility in agarose gel electrophoresis were increased in the following order: LDL-1>LDL-2>LDL-3>normal LDL, indicating LDL-1 to be the most susceptible to lipid peroxidation. The modified LDL samples were taken up by rat peritoneal macrophages in the same order as listed above.
Taking into account the facts that lipid hydroperoxides generate ·OH and LDL-1 is the most susceptible to lipid peroxidation, this subtraction seems to be more atherogenic than the other LDL subfractions.
