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

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 bar...

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Published in:Journal of neurochemistry 2001-01, Vol.76 (2), p.498-508
Main Authors: Goti, Daniel, Hrzenjak, Andelko, Levak‐Frank, Sanja, Frank, Sasa, Van Der Westhuyzen, Deneys R., Malle, Ernst, Sattler, Wolfgang
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Blood-Brain Barrier - physiology
blood–brain barrier
brain
Brain - blood supply
Capillaries - cytology
Capillaries - metabolism
CD36 Antigens - biosynthesis
CD36 Antigens - genetics
Cells, Cultured
Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges
CHO Cells
CLA‐1
Cricetinae
Endothelium, Vascular - cytology
Endothelium, Vascular - metabolism
Fundamental and applied biological sciences. Psychology
lipoprotein
Lipoproteins, HDL - metabolism
Lipoproteins, HDL3
Membrane Proteins
Receptors, Immunologic
Receptors, Lipoprotein
Receptors, Scavenger
scavenger receptors
Scavenger Receptors, Class B
SR‐BI
Swine
tocopherol
Transfection
Vertebrates: nervous system and sense organs
Vitamin E - metabolism
Vitamin E - pharmacokinetics
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Summary: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.
ISSN:0022-3042
1471-4159
DOI:10.1046/j.1471-4159.2001.00100.x