Apolipoprotein oxidation in the absence of lipid peroxidation enhances LDL uptake by macrophages.
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.
Hunt
J V
JV
Department of Pathology, University of Cambridge, UK.
Bailey
J R
JR
Schultz
D L
DL
McKay
A G
AG
Mitchinson
M J
MJ
D001055:Apolipoproteins B / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D003300:Copper / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D010084:Oxidation-Reduction; D011341:Probucol / Q000494:pharmacology
D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D003300:Copper; D006861:Hydrogen Peroxide; D011341:Probucol