ATP-binding cassette transporter A1: regulation of cholesterol efflux.
The ATP-binding cassette transporter A1 (ABCA1) is involved in the regulation of cholesterol efflux from cells. Mutations in ABCA1 give rise to familial high-density lipoprotein (HDL) deficiency and Tangier disease, which is characterized by very low levels of HDL in plasma and cholesteryl ester accumulation in tonsils and other reticuloendothelial cells. The mechanism of action of ABCA1 is still unclear, but requires the transfer of phospholipid and cholesterol to apolipoprotein A1 bound by or close to the transporter. An important factor in the regulation of ABCA1 is cholesterol itself, which provides oxysterol ligands for liver X receptors that stimulate ABCA1 transcription. ABCA1-deficient mice show increased cholesterol absorption, suggesting that ABCA1 could also help to transport dietary cholesterol back out of intestinal absorptive cells into the lumen. Thus ABCA1 is intimately connected to various aspects of the regulation of whole-body cholesterol metabolism and probably plays an important role in protecting against the development of cardiovascular disease.
Knight
B L
BL
MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital, DuCane Road, London W12 ONN, UK. brian.knight@csc.mrc.ac.uk
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000042:Absorption; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic
D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol