ATP-binding Cassette Transporter A1 Mediates Cellular Secretion of α-Tocopherol

Abstract

α-Tocopherol (α-TOH) is associated with plasma lipoproteins and accumulates in cell membranes throughout the body, suggesting that lipoproteins play a role in transporting α-TOH between tissues. Here we show that secretion of α-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 α-TOH efflux. ApoA-I lacked the ability to remove α-TOH from Tangier disease fibroblasts that have a nonfunctional ABCA1. BHK cells that lack an active ABCA1 pathway markedly increased secretion of α-TOH to apoA-I when forced to express ABCA1. ABCA1 also mediated a fraction of the α-TOH efflux promoted by lipid-containing HDL particles, indicating that HDL promotes α-TOH efflux by both ABCA1-dependent and -independent processes. Exposing apoA-I to ABCA1-expressing cells did not enhance its ability to remove α-TOH from cells lacking ABCA1, consistent with this transporter participating directly in the translocation of α-TOH to apolipoproteins. These studies provide evidence that ABCA1 mediates secretion of cellular α-TOH into the HDL metabolic pathway, a process that may facilitate vitamin transport between tissues and influence lipid oxidation.