H. Kuhn et al., OXIDATIVE MODIFICATION OF HUMAN LIPOPROTEINS BY LIPOXYGENASES OF DIFFERENT POSITIONAL SPECIFICITIES, Journal of lipid research, 35(10), 1994, pp. 1749-1759
Cellular lipoxygenases have been implicated in foam cell formation dur
ing the early stages of atherogenesis. We studied the interaction of l
ipoxygenases of different positional specificities with human lipoprot
eins and found that the arachidonate 15-lipoxygenases of rabbit and hu
mans and the arachidonate 12-lipoxygenase of porcine leukocytes oxygen
ate lipoproteins as indicated by the formation of oxygenated lipids an
d changes in electrophoretic mobility of low density lipoprotein. The
arachidonate 12-lipoxygenase of human platelets, the recombinant arach
idonate 5-lipoxygenase of human leukocyte, and the soybean lipoxygenas
e I were less effective in oxidizing human LDL. As a major oxygenation
product, esterified 13S-hydro(pero)xy-9Z,11E-octadecadienoic acid was
identified for both the rabbit reticulocyte 15- and the porcine leuko
cyte 12-lipoxygenase. In addition, esterified -hydro(pero)xy-5,8,11,13
(Z,Z,Z,E)-eicosatetraenoic acid (for the rabbit 15-lipoxygenase) and -
hydro(pero)xy-5,8,10,14(Z,Z,E,Z)-eicosatetraenoic acid (for the porcin
e 12-lipoxygenase) as well as small amounts of racemic 9-hydro(pero)xy
-10,12-octadecadienoic acid isomers were detected. More than 90% of th
e oxygenated polyenoic fatty acids were found in the ester lipid fract
ion, particularly in the cholesteryl esters and in various phospholipi
d classes (phosphatidylcholine and phosphatidylethanolamine). The poss
ible biological significance of lipoxygenase-induced oxidative modific
ation of lipoproteins in the pathogenesis of atherosclerosis is discus
sed.