Influence of apolipoprotein E genotype and dietary α-tocopherol on redox status and C-reactive protein levels in apolipoprotein E3 and E4 targeted replacement mice
The molecular basis of the positive association between apoE4 genotype and CVD remains unclear. There is direct in vitro evidence indicating that apoE4 is a poorer antioxidant relative to the apoE3 isoform, with some indirect in vivo evidence also available. Therefore it was hypothesised that apoE4...
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Published in | British journal of nutrition Vol. 100; no. 1; pp. 44 - 53 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Cambridge, UK
Cambridge University Press
01.07.2008
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Subjects | |
Online Access | Get full text |
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Summary: | The molecular basis of the positive association between apoE4 genotype and CVD remains unclear. There is direct in vitro evidence indicating that apoE4 is a poorer antioxidant relative to the apoE3 isoform, with some indirect in vivo evidence also available. Therefore it was hypothesised that apoE4 carriers may benefit from α-tocopherol (α-Toc) supplementation. Targeted replacement mice expressing the human apoE3 and apoE4 were fed with a diet poor (0 mg/kg diet) or rich (200 mg/kg diet) in α-Toc for 12 weeks. Neither apoE genotype nor dietary α-Toc exerted any effects on the antioxidant defence system, including glutathione, catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase activities. In addition, no differences were observed in mitogen-induced lymphocyte proliferation. α-Toc concentrations were modestly higher in plasma and lower in tissues of apoE4 compared with apoE3 mice, with the greatest differences evident in the lung, suggesting that an apoE4 genotype may reduce α-Toc delivery to tissues. A tendency towards increased plasma F2-isoprostanes in apoE4 mice was observed, while liver thiobarbituric acid-reactive substances did not differ between apoE3 and apoE4 mice. In addition, C-reactive protein (CRP) concentrations were reduced in apoE4 mice indicating that this positive effect on CRP may in part negate the increased CVD risk associated with an apoE4 genotype. |
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Bibliography: | istex:87C66CBF8A57D076C519FE0A5D31B9E12DA893C0 PII:S000711450788634X ark:/67375/6GQ-5L37ZLF7-N Abbreviations: α-Toc, α-tocopherol; CAT, catalase; Con A, concanavalin A; CRP, C-reactive protein; GPx, glutathione peroxidase; GR, glutathione reductase; GSH, glutathione; LPS, lipopolysaccharide; SOD, superoxide dismutase; SRB1, scavenger receptor class B type 1; TBARS, thiobarbituric acid-reactive substances ArticleID:88634 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0007-1145 1475-2662 |
DOI: | 10.1017/S000711450788634X |