BACKGROUND ATP-binding cassette transporter A1 (ABCA1) is a key mediator of cholesterol efflux to apoA-I in cholesterol loaded macrophages, a first step of reverse cholesterol transport (RCT) in vivo. Macrophage specific abca1 inactivation or overexpression, respectively, accelerated or suppressed the development of atherosclerosis in mouse models. However, it is yet to be established that the ...

OBJECTIVE Calpain-mediated proteolysis is one of the major regulatory factors for activity of ATP-binding cassette transporter (ABC) A1. Helical apolipoproteins protect ABCA1 against this degradation and increase generation of HDL. We investigated the mechanism for this reaction focusing on roles of endocytotic internalization of ABCA1. METHODS AND RESULTS Surface ABCA1 was labeled with bioti...

ATP-binding cassette protein A1 (ABCA1) plays a major role in cholesterol homeostasis and high density lipoprotein metabolism. Apolipoprotein A-I binds to ABCA1 and cellular cholesterol and phospholipids, mainly phosphatidylcholine, are loaded onto apoA-I to form pre-beta high density lipoprotein (HDL). It is proposed that ABCA1 translocates phospholipids and cholesterol directly or indirectly ...

ATP-binding cassette transporter A1 (ABCA1) promotes the efflux of cellular cholesterol and phospholipids to apoA-I. We described previously a cytoplasmic PEST sequence in ABCA1 and showed that deletion of the PEST sequence results in a prominent increase in the cell surface concentration of ABCA1. In the current study we evaluated the hypothesis that the PEST sequence-deleted ABCA1 might displ...

ABCA1 mediates the transport of cellular cholesterol and phospholipids to HDL apolipoproteins. Apolipoprotein A-I (apoA-I) interactions with ABCA1-expressing cells elicit several responses, including removing cellular lipids, stabilizing ABCA1 protein, and activating Janus kinase 2 (JAK2). Here, we used synthetic apolipoprotein-mimetic peptides to characterize the relationship between these res...

We report increased cholesterol efflux from macrophages in the presence of falcarindiol, an important dietary constituent present in commonly used vegetables and medicinal plants. Falcarindiol (3-20 μM) increased cholesterol efflux from THP-1-derived macrophages. Western blot analysis showed an increased protein level of ABCA1 upon falcarindiol exposure. Quantitative real-time PCR revealed that...

BACKGROUND AND PURPOSE The ATP-binding cassette transporter A1 (ABCA1) facilitates cholesterol efflux from cells, a key process in reverse cholesterol transport. Whereas previous investigations focused on mutations causing impaired ABCA1 function, we assessed the role of ABCA1 in human carotid atherosclerotic disease. METHODS We compared the mRNA and protein levels of ABCA1, and one of its ke...

Low HDL is a risk factor for the development of type 2 diabetes. Hepatic ABCA1 is the rate-limiting protein in HDL biogenesis, and mice lacking hepatic ABCA1 (ABCA1(-l/-l)) have very low plasma HDL concentrations. To investigate the role of hepatic ABCA1 in glucose tolerance and β-cell function, we used ABCA1(-l/-l) mice, which showed impaired glucose tolerance without changes in insulin sensit...

OBJECTIVE Macrophage expression of both apolipoprotein E (apoE) and ABCA1 have been shown to modulate lipid efflux from these cells and to play an important atheroprotective role in vivo. We evaluated the relationship between apoE and ABCA1 for regulating cellular sterol efflux. METHODS AND RESULTS ApoE-mediated, but ABCA1-independent, lipid efflux was demonstrated in 3 model systems. First, ...