Apolipoprotein oxidation in the absence of lipid peroxidation enhances LDL uptake by macrophages

• Published in: FEBS letters Vol. 349; no. 3; pp. 375 - 379
• Main Authors: Hunt, James V., Bailey, James R., Schultz, Donna L., McKay, Alan G., Mitchinson, Malcolm J.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 08.08.1994
• Subjects: Apolipoproteins B - drug effects; Apolipoproteins B - metabolism; Biological Transport; Cell Line; Copper - pharmacology; Humans; Hydrogen Peroxide - pharmacology; Lipid Peroxidation; Lipoproteins, LDL - metabolism; Low density lipoprotein; Macrophage uptake; Macrophages - metabolism; Oxidation-Reduction; Probucol; Probucol - pharmacology; Protein oxidation; Probucol; Macrophage uptake; Protein oxidation; Low density lipoprotein
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(94)00706-3

A characteristic of the antioxidant, probucol, is its inability to inhibit apolipoprotein B fragmentation in low density lipoprotein (LDL), despite a pronounced ability to inhibit lipid oxidation on relatively lengthy exposure to Cu(II). Here we show that a short exposure of LDL to hydrogen peroxide and Cu(II) leads to 125I-labelled apolipoprotein B fragmentation, the production of malondialdehyde and hydroperoxides and leads to increased uptake by macrophages on subsequent culture. However, pre-loading LDL with probucol protects LDL from lipid oxidation but not protein fragmentation or macrophage uptake. The use of probucol to conduct studies on apolipoprotein B oxidation without extensive lipid oxidation may prove useful when studying LDL apolipoprotein damage on exposure to an aqueous free radical insult.