Peer-Reviewed Journal Details
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Lyons, NM,Woods, JA,O'Brien, NM;
2001
January
Free Radical Research
alpha-Tocopherol, but not gamma-tocopherol inhibits 7 beta-hydroxycholesterol-induced apoptosis in human U937 cells
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oxysterol 7 beta-hydroxycholesterol apoptosis alpha-tocopherol gamma-tocopherol U937 cells HUMAN ENDOTHELIAL-CELLS A REDUCTASE-ACTIVITY SMOOTH-MUSCLE CELLS CHOLESTEROL OXIDATION 7-KETOCHOLESTEROL-INDUCED APOPTOSIS OXYSTEROLS ATHEROSCLEROSIS PLASMA GLUTATHIONE OXIDE
35
329
339
Oxysterols, particularly those oxidised at position 7, are toxic to cells in culture and have been shown to induce apoptosis in cell types such as vascular endothelial cells, smooth muscle cells and monocytes. The precise mechanism by which oxysterols induce apoptosis is unknown but may involve the generation of oxidative stress. In the present study we examined the ability of alpha -TOC, alpha -TOC acetate (alpha -TOCA) and gamma -TOC to protect against 7 beta -hydroxycholesterol (7 beta -OHC)-induced apoptosis of human monocytic U937 cells. 7 beta -OHC is one of the most commonly detected oxysterols in foods and its level in plasma has been positively associated with an increased risk of atherosclerosis.The present study demonstrates a significant decrease in cell membrane integrity and cellular glutathione levels when U937 cells were treated with 30 muM 7 beta -OHC. DNA fragmentation also occurred, as measured by agarose gel electrophoresis, and the number of apoptotic cells increased as assessed by nuclear morphology. Analysis by HPLC showed that there was a greater incorporation of gamma -TOC into U937 cells after a 48 h incubation, than either alpha -TOC or alpha -TOCA. However, despite the increased uptake of gamma -TOC, only alpha -TOC, and not gamma -TOC or alpha -TOCA was effective at inhibiting 7 beta -OHC-induced apoptosis in U937 cells.
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