Uptake and transport of high‐density lipoprotein (HDL) and HDL‐associated α‐tocopherol by an in vitro blood–brain barrier model

Journal of Neurochemistry - Tập 89 Số 4 - Trang 939-950 - 2004
Zoltán Balázs1,2,3, Ute Panzenboeck1,2, Astrid Hammer4, Andrea Sovic2, Oswald Quehenberger5, Ernst Malle2, Wolfgang Sattler2
1Both authors contributed equally.
2Institute of Molecular Biology and Biochemistry
3The present address of Zoltan Balazs is the Department of Clinical Research, Division of Nephrology, University Children's Hospital, Berne, Switzerland.
4Institute of Histology and Embryology, Medical University Graz, Graz, Austria
5Department of Medicine, University of California, San Diego, La Jolla, California, USA

Tóm tắt

AbstractThe present study aimed to investigate pathways that contribute to uptake and transcytosis of high‐density lipoproteins (HDLs) and HDL‐associated α‐tocopherol (αTocH) across an in vitro model of the blood–brain barrier (BBB). In primary porcine brain capillary endothelial cells HDL‐associated αTocH was taken up in 10‐fold excess of HDL holoparticles, indicating efficient selective uptake, a pathway mediated by scavenger receptor class B, type I (SR‐BI). SR‐BI was present in caveolae of brain capillary endothelial cells and expressed almost exclusively at the apical membrane. Disruption of caveolae with methyl‐β‐cyclodextrin (CDX) resulted in (mis)sorting of SR‐BI to the basolateral membrane. Immunohistochemistry of porcine brain cryosections revealed SR‐BI expression on brain capillary endothelial cells and presumably astrocytic endfeet. HDL‐associated [14C]αTocH taken up by brain capillary endothelial cells was recovered in sucrose gradient fractions containing the majority of cellular caveolin‐1, the major caveolae‐associated protein. During mass transfer studies using αTocH‐enriched HDL, approximately 50% of cellular αTocH was recovered with the bulk of cellular caveolin‐1 and SR‐BI. Efflux experiments revealed that a substantial amount of cell‐associated [14C]αTocH could be mobilized into the culture medium. In addition, apical‐to‐basolateral transport of HDL holoparticles and HDL‐associated αTocH was saturable. Results from the present study suggest that part of cerebral apolipoprotein A‐I and αTocH originates from plasma HDL transcytosed across the BBB and that caveolae‐located SR‐BI facilitates selective uptake of HDL‐associated αTocH at the BBB.

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Journal of Neurochemistry

Tập 89 Số 4

939-950

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