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Selected Publication:
Goti, D; Hrzenjak, A; Levak-Frank, S; Frank, S; van der Westhuyzen, DR; Malle, E; Sattler, W.
Scavenger receptor class B, type I is expressed in porcine brain capillary endothelial cells and contributes to selective uptake of HDL-associated vitamin E.
J Neurochem. 2001; 76(2):498-508
Doi: 10.1046%2Fj.1471-4159.2001.00100.x
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- Leading authors Med Uni Graz
- Sattler Wolfgang
- Co-authors Med Uni Graz
- Frank Sasa
- Hrzenjak Andelko
- Levak Sanja
- Malle Ernst
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- Abstract:
- It is clearly established that an efficient supply to the brain of alpha-tocopherol (alphaTocH), 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 alphaTocH 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 alphaTocH 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 alphaTocH 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 alphaTocH 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 alphaTocH 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]alphaTocH 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 alphaTocH uptake. The results of this study indicate that SR-BI promotes the uptake of HDL-associated alphaTocH into cells constituting the BBB and plays an important role during the supply of the CNS with this indispensable micronutrient.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antigens, CD36 - biosynthesis
- Blood-Brain Barrier - physiology
- Brain - blood supply
- CHO Cells - blood supply
- Capillaries - cytology
- Cells, Cultured - cytology
- Cricetinae - cytology
- Endothelium, Vascular - cytology
- Lipoproteins, HDL - metabolism
- Lipoproteins, HDL3 - metabolism
- Membrane Proteins - metabolism
- Receptors, Immunologic - metabolism
- Receptors, Lipoprotein - metabolism
- Receptors, Scavenger - metabolism
- Scavenger Receptors, Class B - metabolism
- Swine - metabolism
- Transfection - metabolism
- Vitamin E - metabolism
- Find related publications in this database (Keywords)
- blood-brain barrier
- brain
- CLA-1
- lipoprotein
- SR-BI
- tocopherol