α-Tocopherol modulates the low density lipoprotein receptor of human HepG2 cells

Nutrition Journal

Paul D Roach¹  Cynthia DK Bottema⁴  Andrew M Thomson²  Sebely Pal³ 

[1] CSIRO Human Nutrition, PO Box 1004, SA 5000, Australia;Laboratory for Cancer Medicine and University Department of Medicine, University of Western Australia, Royal Perth Hospital, Perth, Western Australia;Department of Nutrition, Dietetics and Food Sciences, Curtin University of Technology, Perth, Western Australia;Department of Animal Science Waite Campus, University of Adelaide Glen Osmond, SA 5064, Australia

关键词: cholesterol;    HMG-CoA reductase;    HepG2 cells;    LDL receptor;    α-tocopherol;    vitamin E;   

Others  :  1152167
DOI  :  10.1186/1475-2891-2-3

 received in 2002-12-19, accepted in 2003-05-12,  发布年份 2003

【 摘 要 】

The aim of this study was to determine the effects of vitamin E (α-tocopherol) on the low density lipoprotein (LDL) receptor, a cell surface protein which plays an important role in controlling blood cholesterol. Human HepG2 hepatoma cells were incubated for 24 hours with increasing amounts of α, δ, or γ-tocopherol. The LDL receptor binding activity, protein and mRNA, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA, cell cholesterol and cell lathosterol were measured. The effect of α-tocopherol was biphasic. Up to a concentration of 50 μM, α-tocopherol progressively increased LDL receptor binding activity, protein and mRNA to maximum levels 2, 4 and 6-fold higher than control, respectively. The HMG-CoA reductase mRNA and the cell lathosterol concentration, indices of cholesterol synthesis, were also increased by 40% over control by treatment with 50 μM α-tocopherol. The cell cholesterol concentration was decreased by 20% compared to control at 50 μM α-tocopherol. However, at α-tocopherol concentrations higher than 50 μM, the LDL receptor binding activity, protein and mRNA, the HMG-CoA reductase mRNA and the cell lathosterol and cholesterol concentrations all returned to control levels. The biphasic effect on the LDL receptor was specific for α-tocopherol in that δ and γ-tocopherol suppressed LDL receptor binding activity, protein and mRNA at all concentrations tested despite the cells incorporating similar amounts of the three homologues. In conclusion, α-tocopherol, exhibits a specific, concentration-dependent and biphasic "up then down" effect on the LDL receptor of HepG2 cells which appears to be at the level of gene transcription. Cholesterol synthesis appears to be similarly affected and the cell cholesterol concentration may mediate these effects.

【 授权许可】

   
2003 Pal et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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