ATP-binding cassette transporter A1 mediates cellular secretion of alpha-tocopherol.
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.
Oram
J F
JF
Department of Medicine, University of Washington, Seattle, WA 98195, USA. joram@u.washington.edu
Vaughan
A M
AM
Stocker
R
R
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001693:Biological Transport, Active; D006224:Cricetinae; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D011994:Recombinant Proteins / Q000378:metabolism; D013631:Tangier Disease / Q000378:metabolism; D024502:alpha-Tocopherol / Q000378:metabolism*
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D011994:Recombinant Proteins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D024502:alpha-Tocopherol