The kinetics of copper-induced LDL oxidation depend upon its lipid composition and antioxidant content

Copper promotes oxidation of human low-density lipoprotein (LDL) through mo lecular mechanisms that are still under investigation. We employed native h uman LDL, phospholipid-containing delipidated LDL ghosts, or trilinolein-re constituted, phospholipid-containing LDL to investigate both LDL oxidation and the associated process of copper reduction. Both LDL ghosts and trilino lein-reconstituted LDL were devoid of antioxidants and were extremely susce ptible to AAPH-induced oxidation but, paradoxically, were rather resistant to copper-mediated oxidation. The dynamic reduction of Cu(II) to Cu(I) was quantitatively decreased in LDL ghosts and in trilinolein-reconstituted LDL , also lacking the initial rapid reduction and the subsequent inhibition ph ases, due to the absence of endogenous antioxidants. Conversely, the rate o f copper reduction was linear and likely due to lipid peroxides, either alr eady present or formed during copper-induced oxidation. We suggest that cop per undergoes redox transitions in LDL by utilizing reducing equivalents or iginating from endogenous antioxidants and/or from lipid peroxides in the L DL lipid core. (C) 2000 Academic Press.