OXIDATION OF LOW-DENSITY-LIPOPROTEIN BY IRON OR COPPER AT ACIDIC PH

Oxidized low density lipoprotein (LDL) may play a significant role in atherosclerosis. We have investigated the effect of pH on the oxidatio n of LDL by iron or copper. When LDL was oxidized by iron in the prese nce of cysteine in either Hanks' balanced salt solution (HBSS) or Ham' s F-10 medium, an acidic pH greatly decreased the lag period and incre ased the rate of formation of hydroperoxides and thiobarbituric acid-r eactive substances (TEARS), and increased its uptake by macrophages. T here was a dose-dependent increase of LDL oxidation at acidic pH in th e presence of increasing concentrations of cysteine. When LDL was oxid ized by copper in HBSS, an acidic pH increased the lag phase before th e rapid formation of conjugated dienes, hydroperoxides, and TEARS, but increased its uptake by macrophages. Similar results were obtained us ing Ham's F-10 medium. Cysteine (100 mu m) inhibited the modification of LDL by copper in HBSS at both pH 7.4 and 5.5. As atherosclerotic le sions may be acidic, these observations may help to explain why LDL ox idation occurs locally at these sites.