ABCA1, from pathology to membrane function

Abstract

The ABCA1 transporter is the prototype of the A class of mammalian adenosine triphosphate binding cassette transporters and one of the largest members of this family. ABCA1 has been originally identified as an engulfment receptor on macrophages and, more recently, it has been shown to play an essential role in the handling of cellular lipids. Indeed by promoting the effluxes of membrane phospholipids and cholesterol to lipid-poor apoprotein acceptors, ABCA1 controls the formation of high-density lipoproteins and thus the whole process of reverse cholesterol transport. A number of additional phenotypes have been found in the mouse model of invalidation of the ABCA1 gene. In spite of their clinical diversity, they all are extremely sensitive to variations in the physicochemical properties of the cell membrane, which ABCA1 controls as a lipid translocator.

Rutaecarpine suppresses atherosclerosis in ApoE−/− mice through upregulating ABCA1 and SR-BI within RCT

“…It promotes cholesterol and phospholipid effl ux from cells to lipid-poor ApoA-I and facilitates RCT. Loss-of-function mutations in the ABCA1 gene result in Tangier disease, showing plasma defi ciency of HDL and increase susceptibility to atherosclerosis (8)(9)(10)(11). Transgenic mice that expressed a high level of ABCA1 had increased cholesterol effl ux in macrophages and exhibited a low incidence of developing atherosclerosis ( 12,13 ).…”

Improved fluorescent (calcium indicator) dye uptake in brain slices by blocking multidrug resistance transporters

“…ABC transporters utilize the energy of ATP hydrolysis to pump a wide variety of molecules across extra-and intracellular membranes (Higgins, 1992;Childs and Ling, 1994;Dean et al, 2001;Linton and Higgins, 2007). Their substrates include phospholipids, ions, peptides, steroids, polysaccharides, amino acids, organic anions, bile acids, drugs and other xenobiotics (Higgins, 1992;Borst and Elferink, 2002;Zarubica et al, 2007;Herget and Tampe, 2007;Stieger et al, 2007;Nies and Keppler, 2007). ABC transporters involved in the transport of xenobiotics include but are not limited to P-glycoprotein (Pgp), multidrug resistance associated proteins (MRPs) and the breast cancer resistance protein (BCRP) (Borst and Elferink, 2002).…”

Impaired serum cholesterol efflux capacity in rheumatoid arthritis and systemic lupus erythematosus

“…For example, tumour necrosis factor α is able to reduce the expression of cholesterol transporters,18 myeloperoxidase may alter apoA-I and impair cholesterol efflux,19 20 the activation of Toll-like receptors increases cholesterol uptake,21 and proliferative stimuli increase cholesterol synthesis and reduce cholesterol efflux 22…”