ATP-binding cassette transporter A1 mediates cellular secretion of α-tecopherol

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-1-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-1 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-1 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.