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

J Neurochem. 2004 May;89(4):939-50. doi: 10.1111/j.1471-4159.2004.02373.x.


The present study aimed to investigate pathways that contribute to uptake and transcytosis of high-density lipoproteins (HDLs) and HDL-associated alpha-tocopherol (alpha TocH) across an in vitro model of the blood-brain barrier (BBB). In primary porcine brain capillary endothelial cells HDL-associated alpha TocH 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-beta-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 [(14)C]alpha TocH 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 alpha TocH-enriched HDL, approximately 50% of cellular alpha TocH was recovered with the bulk of cellular caveolin-1 and SR-BI. Efflux experiments revealed that a substantial amount of cell-associated [(14)C]alpha TocH could be mobilized into the culture medium. In addition, apical-to-basolateral transport of HDL holoparticles and HDL-associated alpha TocH was saturable. Results from the present study suggest that part of cerebral apolipoprotein A-I and alpha TocH originates from plasma HDL transcytosed across the BBB and that caveolae-located SR-BI facilitates selective uptake of HDL-associated alpha TocH at the BBB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoprotein A-I / metabolism
  • Biological Transport / physiology
  • Biotinylation
  • Blood-Brain Barrier / cytology
  • Blood-Brain Barrier / metabolism*
  • Brain / cytology
  • Brain / metabolism
  • Brain Chemistry
  • CD36 Antigens
  • Capillaries / cytology
  • Capillaries / metabolism
  • Caveolae / chemistry
  • Caveolae / drug effects
  • Caveolae / metabolism
  • Caveolin 1
  • Caveolins / chemistry
  • Caveolins / metabolism
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cyclodextrins / chemistry
  • Endothelial Cells / metabolism*
  • Lipoproteins, HDL / chemistry
  • Lipoproteins, HDL / metabolism*
  • Models, Biological
  • Receptors, Immunologic / metabolism
  • Receptors, Scavenger
  • Scavenger Receptors, Class B
  • Subcellular Fractions / chemistry
  • Swine
  • alpha-Tocopherol / chemistry
  • alpha-Tocopherol / metabolism*
  • beta-Cyclodextrins*


  • Apolipoprotein A-I
  • CD36 Antigens
  • Caveolin 1
  • Caveolins
  • Cyclodextrins
  • Lipoproteins, HDL
  • Receptors, Immunologic
  • Receptors, Scavenger
  • Scavenger Receptors, Class B
  • beta-Cyclodextrins
  • methyl-beta-cyclodextrin
  • alpha-Tocopherol