Abstract

Despite the physiologic importance of vitamin E, in particular its ?-tocopherol (?-T) isoform, the molecular mechanisms involved in the cellular uptake of this antioxidant from plasma lipoproteins have not been well-defined. Recent studies have suggested that selective lipid uptake, rather than endocytosis, is important for ?-T delivery to cells. Here we show that the scavenger receptor class B type I (SR-BI), which mediates cellular selective cholesteryl ester uptake from lipoproteins, facilitates efficient transfer of ?-T from HDL to cultured cells. In SR-BI-deficient mutant mice, relative to wild-type control animals, there was a significant increase in plasma ?-T levels (1.1- to 1.4-fold higher) that was mostly due to the elevated ?-T content of their abnormally large plasma HDL-like particles. This increase in plasma ?-T in SR-BI knockout mice was accompanied by a significant decrease (65-80%) in the ?-T concentrations in bile and several tissues including ovary, testis, lung and brain. SR-BI deficiency did not alter the ?-T concentrations of the liver, spleen, kidney or white fat. These data show that SR-BI plays an important role in transferring ?-T from plasma lipoproteins to specific tissues. Also, in the case of the liver as was previously shown for SR-BI-dependent hepatic cholesterol transport, SR-BI-mediated uptake of ?-T was primarily coupled to biliary excretion rather than to tissue accumulation. Defective tissue uptake of lipoprotein ?-T in SR-BI-deficient mice may contribute to the reproductive and cardiovascular pathologies exhibited by these animals.