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.