Scavenger receptor class B, type I is expressed in porcine brain capillaryendothelial cells and contributes to selective uptake of HDL-associated vitamin E

It is clearly established that an efficient supply to the brain of alpha -t ocopherol (alpha TocH), the most biologically active member of the Vitamin E family, is of the utmost importance for proper neurological functioning. Although the mechanism of uptake of alpha TocH into cells constituting the brood-brain barrier (BBB) is obscure, we previously demonstrated that high- density lipoprotein (HDL) plays a major role in the supply of alpha TocH to porcine brain capillary endothelial cells (pBCECs). Here we studied whethe r a porcine analogue of human and rodent scavenger receptor class B, type I mediates selective (without concomitant lipoprotein particle internalizati on) uptake of HDL-associated alpha TocH in a similar manner to that describ ed for HDL-associated cholesteryl esters (CEs). In agreement with this hypo thesis we observed that a major proportion of alpha TocH uptake by pBCECs o ccurred by Selective uptake, exceeding HDL3 holoparticle uptake by up to 13 -fold. The observation that selective uptake of MDL-associated CE exceeded HDL3 holoparticle up to fourfold Suggested that a porcine analogue of SR-BI (pSR-BI) may be involved in lipid uptake at the BBB. In line with the obse rvation of selective lipid uptake, RT-PCR and northern and western blot ana lyses revealed the presence of pSR-BI in cells constituting the BBB. Adenov irus-mediated overexpression of the human analogue of SR-BI (hSR-BI) in pBC ECs resulted in a fourfold increase in selective HDL-associated alpha TocH uptake. In accordance with the proposed function of SR-BI, selective HDL-CE uptake was increased sixfold in Chinese hamster ovary cells stably transfe cted with murine SR-BI (mSR-BI). Most importantly stable mSR-BI overexpress ion mediated a twofold increase in HDL-associated [C-14]alpha TocH selectiv e uptake in comparison with control cells. In line with tracer experiments, mass transfer studies with unlabelled lipoproteins revealed that mSR-BI ov erexpression resulted in a twofold increase in endogenous HDL3-associated a lpha TocH uptake. The results of this Study indicate that SR-BI promotes th e uptake of HDL-associated alpha TocH into cells constituting the BBB and p lays an important role during the supply of the CNS with this indispensable micronutrient.