Physical partitioning is the main mechanism of α-tocopherol and cholesterol transfer between lipoproteins and P388D1 macrophage-like cells

Relo Asmis

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Abstract

The regulation of cellular vitamin E concentration was studied in P388D1 macrophage-like cells. Cellular α-tocopherol levels increased more than 5000-fold over constitutive levels without reaching saturation when P388D1 cells were cultured in vitamin-E-supplemented fetal calf serum. The uptake of α-tocopherol was accompanied by accumulation of α-[3H]tocopherol and [14C]cholesterol in these cells. Human unmodified low-density lipoprotein (LDL) inhibited the uptake of α-[3H]tocopherol and [14C]cholesterol in a dose-dependent manner and with very similar IC50. Acetylated, Cu2+-oxidized and aggregated human LDL and human very-low-density-lipoprotein (VLDL) were similarly potent, whereas human HDL was at least tenfold less effective than human LDL when inhibitory activity was correlated to lipoprotein protein levels. The rate of vitamin E uptake by P388D1 cells, however, always correlated with the extracellular α-tocopherol/cholesterol ratio. Efflux of α-[3H]tocopherol from labeled P388D1 cells required extracellular accepters and was accompanied by the concomitant release of [14C]cholesterol. Both human LDL and HDL could serve as accepters. Changes in the cellular a-tocopherol level appear to be the direct consequence of changes in the extracellular α-tocopherol/cholesterol ratio due to a rapid exchange of lipids between P38D1 cells and their extracellular environment. While the transfer of α-tocopherol from LDL, VLDL, and fetal calf serum into P388D1 cells appears to occur mainly by diffusion, HDL-stimulated efflux of α-tocopherol may underlie a different mechanism. The α-tocopherol/ cholesterol ratio of the extracellular environment may be a critical factor in determining cellular vitamin E levels in vivo.

Original languageEnglish (US)
Pages (from-to)600-607
Number of pages8
JournalEuropean Journal of Biochemistry
Volume250
Issue number2
DOIs
Publication statusPublished - Jan 1 1997

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Keywords

  • Antioxidant
  • Atherosclerosis
  • Foam cell formation
  • Low-density lipoprotein
  • Vitamin E

ASJC Scopus subject areas

  • Biochemistry

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