Time course of oxysterol formation during in vitro oxidation of low density lipoprotein

被引:73
作者
Dzeletovic, S [1 ]
Babiker, A [1 ]
Lund, E [1 ]
Diczfalusy, U [1 ]
机构
[1] KAROLINSKA INST,HUDDINGE UNIV HOSP,DIV CLIN CHEM,DEPT MED LAB SCI & TECHNOL,S-14186 HUDDINGE,SWEDEN
关键词
soybean lipoxygenase; copper oxidation; cholesterol; cholesterol-7-hydroperoxides; fatty acids;
D O I
10.1016/0009-3084(95)02489-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cholesterol oxidation products (oxysterols) have been implicated in several aspects of atherogenesis; they affect key enzymes in cholesterol homeostasis, induce calcification in vascular cells and possess cytotoxic properties. Oxysterols are formed during oxidative modification of low density lipoprotein (LDL). Using a recently developed method based on isotope dilution-mass spectrometry, the kinetics of formation of oxysterols during oxidation of LDL by cupric ions or soybean lipoxygenase was studied. The same products, mainly 7- and 5-oxygenated cholesterol, were formed by the two oxidation methods. Virtually no side-chain oxidized oxysterols were formed. During the oxidations, preferentially esterified cholesterol was consumed and consumption of polyunsaturated fatty acids and formation of conjugated dienes preceded the appearance of oxysterols. Cholesterol 7-hydroperoxides potential cytotoxins, were present in LDL oxidized by copper or lipoxygenase.
引用
收藏
页码:119 / 128
页数:10
相关论文
共 34 条
[1]   THE MECHANISMS OF THE REARRANGEMENTS OF ALLYLIC HYDROPEROXIDES - 5-ALPHA-HYDROPEROXY-3-BETA-HYDROXYCHOLEST-6-ENE AND 7-ALPHA-HYDROPEROXY-3-BETA-HYDROXYCHOLEST-5-ENE [J].
BECKWITH, ALJ ;
DAVIES, AG ;
DAVISON, IGE ;
MACCOLL, A ;
MRUZEK, MH .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, 1989, (07) :815-824
[2]   OXYGENATION OF LIPOPROTEINS BY MAMMALIAN LIPOXYGENASES [J].
BELKNER, J ;
WIESNER, R ;
RATHMAN, J ;
BARNETT, J ;
SIGAL, E ;
KUHN, H .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1993, 213 (01) :251-261
[3]   OXIDATION OF CHOLESTEROL MOIETY OF LOW-DENSITY-LIPOPROTEIN IN THE PRESENCE OF HUMAN ENDOTHELIAL-CELLS OR CU+2 IONS - IDENTIFICATION OF MAJOR PRODUCTS AND THEIR EFFECTS [J].
BHADRA, S ;
ARSHAD, MAQ ;
RYMASZEWSKI, Z ;
NORMAN, E ;
WHERLEY, R ;
SUBBIAH, MTR .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 176 (01) :431-440
[4]   PRODUCTION OF OXIDIZED LIPIDS DURING MODIFICATION OF LOW-DENSITY-LIPOPROTEIN BY MACROPHAGES OR COPPER [J].
CARPENTER, KLH ;
WILKINS, GM ;
FUSSELL, B ;
BALLANTINE, JA ;
TAYLOR, SE ;
MITCHINSON, MJ ;
LEAKE, DS .
BIOCHEMICAL JOURNAL, 1994, 304 :625-633
[5]  
CATHCART MK, 1991, J LIPID RES, V32, P63
[6]  
Chait A, 1992, CURR OPIN LIPIDOL, V3, P389
[7]   7-BETA-HYDROPEROXYCHOLEST-5-EN-3-BETA-OL, A COMPONENT OF HUMAN ATHEROSCLEROTIC LESIONS, IS THE PRIMARY CYTOTOXIN OF OXIDIZED HUMAN LOW-DENSITY-LIPOPROTEIN [J].
CHISOLM, GM ;
MA, GP ;
IRWIN, KC ;
MARTIN, LL ;
GUNDERSON, KG ;
LINBERG, LF ;
MOREL, DW ;
DICORLETO, PE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (24) :11452-11456
[8]   DETERMINATION OF CHOLESTEROL OXIDATION-PRODUCTS IN HUMAN PLASMA BY ISOTOPE-DILUTION MASS-SPECTROMETRY [J].
DZELETOVIC, S ;
BREUER, O ;
LUND, E ;
DICZFALUSY, U .
ANALYTICAL BIOCHEMISTRY, 1995, 225 (01) :73-80
[9]  
Esterbauer Hermann, 1993, Current Opinion in Lipidology, V4, P114, DOI 10.1097/00041433-199304000-00007
[10]   CYTOTOXICITY OF OXIDIZED LDL TO PORCINE AORTIC SMOOTH-MUSCLE CELLS IS ASSOCIATED WITH THE OXYSTEROLS 7-KETOCHOLESTEROL AND 7-HYDROXYCHOLESTEROL [J].
HUGHES, H ;
MATHEWS, B ;
LENZ, ML ;
GUYTON, JR .
ARTERIOSCLEROSIS AND THROMBOSIS, 1994, 14 (07) :1177-1185