出版社：American Society for Biochemistry and Molecular Biology
摘要：In hepatocytes, vitamin E is secreted via the efflux pathwayand is believed to associate with apolipoprotein B (apoB)-lipoproteinsextracellularly. The molecular mechanisms involved in the uptake,intracellular trafficking, and secretion of dietary vitaminE by the intestinal cells are unknown. We observed that lowconcentrations of Tween-40 were better for the solubilizationand delivery of vitamin E to differentiated Caco-2 cells, whereashigh concentrations of Tween-40 and sera inhibited this uptake.Vitamin E uptake was initially rapid and then reached saturation.Subcellular localization revealed that vitamin E primarily accumulatedin microsomal membranes. Oleic acid (OA) treatment, which induceschylomicron assembly and secretion, decreased microsomal membrane-boundvitamin E in a time-dependent manner. To study secretion, differentiatedCaco-2 cells were pulse-labeled with vitamin E and chased inthe presence and absence of OA. In the absence of OA, vitaminE was associated with intestinal high density lipoprotein (I-HDL),whereas OA-treated cells secreted vitamin E with I-HDL and chylomicrons.No extracellular transfer of vitamin E between these lipoproteinswas observed. Glyburide, an antagonist of ABCA1, partially inhibitedits secretion with I-HDL, whereas plasma HDL increased vitaminE efflux. An antagonist of microsomal triglyceride transferprotein, brefeldin A, and monensin specifically inhibited vitaminE secretion with chylomicrons. These studies indicate that vitaminE taken up by Caco-2 cells is stored in the microsomal membranesand secreted with chylomicrons and I-HDL. Transport via I-HDLmight contribute to vitamin E absorption in patients with abetalipoproteinemiareceiving large oral doses of the vitamin.Supplementary key words microsomal triglyceride transfer protein • lipoprotein assembly • triglycerides • cholesteryl esters • phospholipids • triacylglycerol • apolipoprotein B • tocopherol • abetalipoproteinemia
Abbreviations: apoB, apolipoprotein B; I-HDL, intestinal high density lipoprotein; MTP, microsomal triglyceride transfer protein; OA, oleic acid; SFM, serum-free medium; TC, taurocholate; TTP, -tocopherol transfer protein
TTP, 
