Cosupplementation with coenzyme Q prevents the prooxidant effect of alpha-tocopherol and increases the resistance of LDL to transition metal-dependent oxidation initiation

被引:132
作者
Thomas, SR [1 ]
Neuzil, J [1 ]
Stocker, R [1 ]
机构
[1] HEART RES INST, BIOCHEM GRP, SYDNEY, NSW 2050, AUSTRALIA
关键词
atherosclerosis; lipid hydroperoxides; macrophage; ubiquinone; vitamin E;
D O I
10.1161/01.ATV.16.5.687
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
There is considerable interest in the ability of antioxidant supplementation, in particular with vitamin E, to attenuate LDL oxidation, a process implicated in atherogenesis. Since vitamin E can also promote LDL lipid peroxidation, we investigated the effects of supplementation with vitamin E alone or in combination with coenzyme Q on the early stages of the oxidation of isolated LDL. Isolated LDL was obtained from healthy subjects before and after in vitro enrichment with vitamin E (D-alpha-tocopherol, alpha-TOH) or dietary supplementation with D-alpha-TOH (1 g/d) and/or coenzyme Q (100 mg/d). LDL oxidation initiation was assessed by measurement of the consumption of alpha-TOH and cholesteryl esters containing polyunsaturated fatty acids and the accumulation of cholesteryl ester hydroperoxides during incubation of LDL in the transition metal-containing Ham's F-10 medium in the absence and presence of human monocyte-derived macrophages (MDMs). Native LDL contained 8.5+/-2 molecules of alpha-TOH and 0.5 to 0.8 molecules of ubiquinol-10 (CoQ(10)H(2), the reduced form of coenzyme Q) per lipoprotein particle. Incubation of this LDL in Ham's F-10 medium resulted in a time-dependent loss of alpha-TOH with concomitant stoichiometric conversion of the major cholesteryl esters to their respective hydroperoxides. MDMs enhanced this process. LDL lipid peroxidation occurred via a radical chain reaction in the presence of alpha-TOH, and the rate of this oxidation decreased on alpha-TOH depletion. In vitro enrichment of LDL with alpha-TOH resulted in an LDL particle containing sixfold to sevenfold more alpha-TOH, and such enriched LDL was more readily oxidized in the absence and presence of MDMs compared with native LDL. In vivo alpha-TOH-deficient LDL, isolated from a patient with familial isolated vitamin E deficiency, was highly resistant to Ham's F-10-initiated oxidation, whereas dietary supplementation with vitamin E restored the oxidizability of the patient's LDL. Oral supplementation of healthy individuals for 5 days with either alpha-TOH or coenzyme Q increased the LDL levels of alpha-TOH and CoQ(10)H(2) by two to three or three to four times, respectively. alpha-TOH-supplemented LDL was significantly more prone to oxidation, whereas CoQ(10)H(2)-enriched LDL was more resistant to oxidation initiation by Ham's F-10 medium than native LDL. Cosupplementation with both alpha-TOH and coenzyme Q resulted in LDL with increased levels of alpha-TOH and CoQ(10)H(2), and such LDL was markedly more resistant to initiation of oxidation than native or alpha-TOH-enriched LDL. These results demonstrate that oral supplementation with alpha-TOH alone results in LDL that is more prone to oxidation initiation, whereas cosupplementation with coenzyme Q not only prevents this prooxidant activity of vitamin E but also provides the lipoprotein with increased resistance to oxidation.
引用
收藏
页码:687 / 696
页数:10
相关论文
共 54 条
[11]  
DIEBERROTHENEDER M, 1991, J LIPID RES, V32, P1325
[12]   ROLE OF VITAMIN-E IN PREVENTING THE OXIDATION OF LOW-DENSITY-LIPOPROTEIN [J].
ESTERBAUER, H ;
DIEBERROTHENEDER, M ;
STRIEGL, G ;
WAEG, G .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 1991, 53 (01) :S314-S321
[13]  
ESTERBAUER H, 1987, J LIPID RES, V28, P495
[14]  
FREI B, 1993, J LIPID RES, V34, P2135
[15]   A COMPARISON OF THE ANTIATHEROGENIC EFFECTS OF PROBUCOL AND OF A STRUCTURAL ANALOG OF PROBUCOL IN LOW-DENSITY-LIPOPROTEIN RECEPTOR-DEFICIENT RABBITS [J].
FRUEBIS, J ;
STEINBERG, D ;
DRESEL, HA ;
CAREW, TE .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (01) :392-398
[16]   LOW-DENSITY LIPOPROTEIN PATHWAY AND ITS RELATION TO ATHEROSCLEROSIS [J].
GOLDSTEIN, JL ;
BROWN, MS .
ANNUAL REVIEW OF BIOCHEMISTRY, 1977, 46 :897-930
[17]  
HANAKI Y, 1991, NEW ENGL J MED, V325, P814
[18]   IRON AND COPPER PROMOTE MODIFICATION OF LOW-DENSITY LIPOPROTEIN BY HUMAN ARTERIAL SMOOTH-MUSCLE CELLS IN CULTURE [J].
HEINECKE, JW ;
ROSEN, H ;
CHAIT, A .
JOURNAL OF CLINICAL INVESTIGATION, 1984, 74 (05) :1890-1894
[19]  
HEINONEN OP, 1994, NEW ENGL J MED, V330, P1029
[20]   AUTOXIDATION OF LIPIDS AND ANTIOXIDATION BY ALPHA-TOCOPHEROL AND UBIQUINOL IN HOMOGENEOUS SOLUTION AND IN AQUEOUS DISPERSIONS OF LIPIDS - UNRECOGNIZED CONSEQUENCES OF LIPID PARTICLE-SIZE AS EXEMPLIFIED BY OXIDATION OF HUMAN LOW-DENSITY-LIPOPROTEIN [J].
INGOLD, KU ;
BOWRY, VW ;
STOCKER, R ;
WALLING, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (01) :45-49