Copper-Modified Low Density Lipoprotein from Diabetic Patients Enhances Cholesteryl Ester Synthesis by Mouse Peritoneal Macrophages

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In this study, the capability of superoxide production by LDL either without stimulation or under the stimulation of Fe-ADP and the manner of modification of low density lipoprotein (LDL) by copper (Cu⁺⁺) in diabetic patients were examined and compared with those of healthy subjects. The amount of superoxide generated by diabetic LDL was similar to that of healthy subjects both at the basal level and following stimulation by Fe-ADP. LDL from healthy subjects and diabetic patients was modified in the presence of 10μM CuSO₄. When the level of thiobarbituric acid-reactive substance was determined in the Cu⁺⁺-modified LDL, no difference was found. On the other hand, when the incorporation of [¹⁴C]oleate into cholesteryl ester (CE) by mouse peritoneal macrophages was stimulated by the Cu⁺⁺-modified LDL, we found that the modified diabetic LDL significantly enhanced the CE synthesis compared with the modified healthy LDL (p<0.01). To clarify the mechanism of the enhanced CE synthesis, the rate of degradation of [¹²⁵I]Cu⁺⁺-modified diabetic LDL was measured. We found that this rate was similar to that of healthy subjects. These data suggest that the degree of oxidation does not differ among patients although diabetic LDL is modified by Cu⁺⁺ in a manner such that it preferentially promotes the activity of CE synthesis in macrophages by some unknown intracellular metabolic mechanism.