LIPOXYGENASE TREATMENT RENDERS LOW-DENSITY-LIPOPROTEIN SUSCEPTIBLE TOCU2-CATALYZED OXIDATION()

Citation
A. Lass et al., LIPOXYGENASE TREATMENT RENDERS LOW-DENSITY-LIPOPROTEIN SUSCEPTIBLE TOCU2-CATALYZED OXIDATION(), Biochemical journal, 314, 1996, pp. 577-585
Citations number
29
Categorie Soggetti
Biology
Journal title
ISSN journal
02646021
Volume
314
Year of publication
1996
Part
2
Pages
577 - 585
Database
ISI
SICI code
0264-6021(1996)314:<577:LTRLST>2.0.ZU;2-Z
Abstract
Oxidative modification of low-density lipoprotein (LDL) has been impli cated in foam-cell formation at all stages of atherosclerosis. Since t ransition metals and mammalian 15-lipoxygenases are capable of oxidizi ng LDL to its atherogenic form, a concerted action of these two cataly sts in atherogenesis has been ted, Cu2+-catalysed LDL oxidation is cha racterized by a kinetic lag period in which the lipophilic antioxidant s are decomposed and by a complex mixture of unspecific oxidation prod ucts. We investigated the kinetics of the 15-lipoxygenase-catalysed ox ygenation of LDL and found that the enzyme is capable of oxidizing LDL in the presence of the endogenous lipophilic antioxidants. In contras t with the Cu2+-catalysed reaction, no kinetic lag phase was detected. The pattern of products formed during short-term incubations was high ly specific, with cholesterol-esterified (13S)-hydroperoxy-(9Z,11E)-oc tadecadienoic acid being the major product. However, after long-term i ncubations the product pattern was less specific. Preincubation with 1 5-lipoxygenase rendered human LDL more susceptible to Cu2+-catalysed o xidation as indicated by a dramatic shortening of the lag period. Addi tion of Cu2+ to lipoxygenase-treated LDL led to a steep decline in its antioxidant content and to a greatly reduced lag period. Interestingl y, if normalized to a comparable hydroperoxide content, autoxidation a nd addition of exogenous hydroperoxy fatty acids both failed to overco me the lag period. The local peroxide concentrations in various LDL su bcompartments will be discussed as a possible reason for this unexpect ed behaviour.