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

D Goti, A Hrzenjak, S Levak‐Frank… - Journal of …, 2001 - Wiley Online Library
D Goti, A Hrzenjak, S Levak‐Frank, S Frank, DR Van Der Westhuyzen, E Malle, W Sattler
Journal of neurochemistry, 2001Wiley Online Library
It is clearly established that an efficient supply to the brain of α‐tocopherol (αTocH), 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 αTocH into cells constituting
the blood–brain barrier (BBB) is obscure, we previously demonstrated that high‐density
lipoprotein (HDL) plays a major role in the supply of αTocH to porcine brain capillary
endothelial cells (pBCECs). Here we studied whether a porcine analogue of human and …
It is clearly established that an efficient supply to the brain of α‐tocopherol (αTocH), 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 αTocH into cells constituting the blood–brain barrier (BBB) is obscure, we previously demonstrated that high‐density lipoprotein (HDL) plays a major role in the supply of αTocH to porcine brain capillary endothelial cells (pBCECs). Here we studied whether a porcine analogue of human and rodent scavenger receptor class B, type I mediates selective (without concomitant lipoprotein particle internalization) uptake of HDL‐associated αTocH in a similar manner to that described for HDL‐associated cholesteryl esters (CEs). In agreement with this hypothesis we observed that a major proportion of αTocH uptake by pBCECs occurred by selective uptake, exceeding HDL3 holoparticle uptake by up to 13‐fold. The observation that selective uptake of HDL‐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 observation of selective lipid uptake, RT‐PCR and northern and western blot analyses revealed the presence of pSR‐BI in cells constituting the BBB. Adenovirus‐mediated overexpression of the human analogue of SR‐BI (hSR‐BI) in pBCECs resulted in a fourfold increase in selective HDL‐associated αTocH uptake. In accordance with the proposed function of SR‐BI, selective HDL–CE uptake was increased sixfold in Chinese hamster ovary cells stably transfected with murine SR‐BI (mSR‐BI). Most importantly stable mSR‐BI overexpression mediated a twofold increase in HDL‐associated [14C]αTocH selective uptake in comparison with control cells. In line with tracer experiments, mass transfer studies with unlabelled lipoproteins revealed that mSR‐BI overexpression resulted in a twofold increase in endogenous HDL3‐associated αTocH uptake. The results of this study indicate that SR‐BI promotes the uptake of HDL‐associated αTocH into cells constituting the BBB and plays an important role during the supply of the CNS with this indispensable micronutrient.
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