Vitamin E Modulates the Expression of the Hepatic Alpha Tocopherol Transfer Protein (TTP)

Abstract

Alpha tocopherol is the most biologically active form of the vitamin E, which is selectively retained in the body. The hepatic tocopherol transfer protein (TTP) regulates body‐wide levels of vitamin E by facilitating the selective secretion of ‐tocopherol from hepatocytes to circulating lipoproteins. We studied whether vitamin E affects the expression of TTP in cultured HepG2 cells engineered to inducibly express the protein. Treatment with vitamin E (100ìM RRR‐alpha‐tocopherol for 48 hours) increased the steady‐state levels of TTP by attenuating the rate at which the protein is degraded by the proteasome. Fractionation studies indicated that treatment with tocopherol induced translocation of a fraction of the TTP protein from the soluble to the insoluble fraction of the cell. In vitro,vitamin E significantly protected TTP against proteolytic degradation by trypsin.These observations suggest that vitamin E imparts a distinct conformation on TTP that is associated with localization to a specific cellular compartment, and with decreased availability for proteasomal degradation.μμαααααα