THERMAL-STABILITY OF APOLIPOPROTEIN B100 IN LOW-DENSITY-LIPOPROTEIN IS DISRUPTED AT EARLY STAGES OF OXIDATION WHILE NEUTRAL LIPID CORE ORGANIZATION IS CONSERVED

The time course of die unfolding characteristics of the protein moiety and of the thermotropic behavior of the core-located apolar lipids of highly homogeneous low-density lipoprotein (LDL) subspecies (d 1.030- 1.040 g/mL) have been evaluated during transition metal-and azo radica l-induced oxidation using differential scanning calorimetry. Apolipopr otein B100 (apo-B100) structure was highly sensitive to oxidative modi fication; indeed, a significant loss of thermal stability was observed at initial stages irrespective of whether oxidation was mediated by s ite-specific binding of copper ions or by free radicals generated duri ng decomposition of azo compounds. Subsequently, thermal protein integ rity was destroyed, as a result of potentially irreversible protein un folding, cross-linking reactions, and aggregation, Our results suggest that even minimal oxidative modification of apo-B100 has a major impa ct on the stability of this large monomeric protein. By contrast, the core lipids, which consist primarily of cholesteryl esters and triglyc erides and play a determinant role in the thermal transition occurring near physiological temperature, preserved features of an ordered arra ngement even during propagation of lipid peroxidation.