Molecular cloning of the human ATP-binding cassette transporter 1 (hABC1):Evidence for sterol-dependent regulation in macrophages

We have cloned the full-length cDNA for the human ATP binding cassette tran sporter 1 (hABC1). The 6603-bp open reading frame encodes a polypeptide of 2201 amino acids resulting in a deduced molecular weight of 220 kDa. The hA BC1 cDNA is highly homologous (62%) to the human rim ABC transporter (ABCR) . hABC1 is expressed in a variety of human tissues with highest expression levels found in placenta, liver, lung, adrenal glands, and fetal tissues. W e demonstrate that the hABC1 expression is induced during differentiation o f human monocytes into macrophages in vitro. In macrophages, both the hABC1 mRNA and protein expression are upregulated in the presence of acetylated low-density lipoprotein (AcLDL). The AcLDL-induced increase in hABC1 expres sion is reversed by cholesterol depletion mediated by the addition of high- density lipoprotein (HDL,). Our data, demonstrating sterol-dependent regula tion of hABC1 in human monocytes/macrophages, suggest a novel role for this transporter molecule in membrane lipid transport. (C) 1999 Academic Press.