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ATP-binding cassette transporter A1 mediates cellular secretion of alpha-tocopherol.

Abstract
Alpha-tocopherol (alpha-TOH) is associated with plasma lipoproteins and accumulates in cell membranes throughout the body, suggesting that lipoproteins play a role in transporting alpha-TOH between tissues. Here we show that secretion of alpha-TOH from cultured cells is mediated in part by ABCA1, an ATP-binding cassette protein that transports cellular cholesterol and phospholipids to lipid-poor high density lipoprotein (HDL) apolipoproteins such as apoA-I. Treatment of human fibroblasts and murine RAW264 macrophages with cholesterol and/or 8-bromo-cyclic AMP, which induces ABCA1 expression, enhanced apoA-I-mediated alpha-TOH efflux. ApoA-I lacked the ability to remove alpha-TOH from Tangier disease fibroblasts that have a nonfunctional ABCA1. BHK cells that lack an active ABCA1 pathway markedly increased secretion of alpha-TOH to apoA-I when forced to express ABCA1. ABCA1 also mediated a fraction of the alpha-TOH efflux promoted by lipid-containing HDL particles, indicating that HDL promotes alpha-TOH efflux by both ABCA1-dependent and -independent processes. Exposing apoA-I to ABCA1-expressing cells did not enhance its ability to remove alpha-TOH from cells lacking ABCA1, consistent with this transporter participating directly in the translocation of alpha-TOH to apolipoproteins. These studies provide evidence that ABCA1 mediates secretion of cellular alpha-TOH into the HDL metabolic pathway, a process that may facilitate vitamin transport between tissues and influence lipid oxidation.
AuthorsJ F Oram, A M Vaughan, R Stocker
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 43 Pg. 39898-902 (Oct 26 2001) ISSN: 0021-9258 [Print] United States
PMID11546785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Apolipoprotein A-I
  • Recombinant Proteins
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Cyclic AMP
  • alpha-Tocopherol
Topics
  • 8-Bromo Cyclic Adenosine Monophosphate (pharmacology)
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters (genetics, metabolism)
  • Animals
  • Apolipoprotein A-I (metabolism)
  • Biological Transport, Active
  • Cricetinae
  • Cyclic AMP (analogs & derivatives, pharmacology)
  • Fibroblasts (metabolism)
  • Humans
  • Macrophages (metabolism)
  • Mice
  • Recombinant Proteins (metabolism)
  • Tangier Disease (metabolism)
  • alpha-Tocopherol (metabolism)

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