OXIDATIVE SUSCEPTIBILITY OF LOW-DENSITY-LIPOPROTEIN SUBFRACTIONS IS RELATED TO THEIR UBIQUINOL-10 AND ALPHA-TOCOPHEROL CONTENT

The conjugated polyene fatty acid parinaric acid (PnA) undergoes a sto ichiometric loss in fluorescence upon oxidation and can be used to dir ectly monitor peroxidative stress within lipid environments. We evalua ted the course of potentially atherogenic oxidative changes in low den sity lipoproteins (LDL) by monitoring the oxidation of PnA following i ts incorporation into buoyant (rho = 1.026-1.032 g/ml) and dense (rho = 1.040-1.054 g/ml) LDL subfractions. Copper-induced oxidation of LDL- associated PnA exhibited an initial lag phase followed by an increased rate of loss until depletion. Increased PnA oxidation occurred immedi ately after the antioxidants ubiquinol-10 and alpha-tocopherol were co nsumed but before there were marked elevations in conjugated dienes. D espite differences in sensitivity to early oxidation events, PnA oxida tion and conjugated diene lag times were correlated (r = 0.582; P = 0. 03), and both indicated a greater susceptibility of dense than buoyant LDL in accordance with previous reports. The greater susceptibility o f PnA in dense LDL was attributed to reduced levels of ubiquinol-10 an d alpha-tocopherol, which were almost-equal-to 50% lower than in buoya nt LDL (mol of antioxidant/mol of LDL) and together accounted for 80% of the variation in PnA oxidation lag times. These results suggest tha t PnA is a useful probe of LDL oxidative susceptibility and may be sup erior to conjugated dienes for monitoring the initial stages of LDL li pid peroxidation. Differences in oxidative susceptibility among LDL de nsity subfractions are detected by the PnA assay and are due in large part to differences in their antioxidant content.