ABCA1 regulation by SREBP-2 and LXR

ATP-binding cassette transporter A1, or ABCA1 is a transmembrane protein expressed by the Golgi complex and plasma membrane, which functions as a cholesterol efflux pump. Regulated by cholesterol flux, it plays an important role in phospholipid homeostasis, regulating cholesterol and lipid removal from the cell. ABCA1 antibody studies by J.Wong et al have shown ABCA1transcription to be regulated by the transcription factors SREBP-2 and LXR.

Cholesterol is an essential cellular component, transported in the bloodstream by high-density or low-density lipoproteins. HDL is responsible for transporting lipids from the cells to the liver for disposal; higher levels are associated with a lowered risk of cardiovascular disease. However, excess LDL can be taken up by macrophages, which then become foam cells – associated with the formation of atheromatous plaques.

Cellular cholesterol levels are under the control of SREBP-2 (sterol-regulatory-element-binding protein-2) and LXR (liver X receptor). SREBP-2 upregulates genes controlling cholesterol biosynthesis and the uptake into the cell, whereas LXR regulates cholesterol efflux genes, including ABCA1. However, in ABCA1 antibody assays, SREBP-2 was shown to down-regulate ABCA1 expression via ABCA1-promoter E-box binding. Statin treatment also caused ABCA1 down-regulation in macrophages; statins induce activation of SREBP-2.

In 2006, J.Wong studied ABCA1 expression in hamster mutant ovary cells. Cells over-expressing SREBP-2 showed increased levels of ABCA1 mRNA, whereas cells deficient in SREBP-2 showed decreased ABCA1 levels. In addition, ABCA1 expression was associated with increased cholesterol synthesis. In a human ABCA1antibody promoter reporter assay, mutation of the promoter SREBP-2 binding site had a similar effect to statin or cholesterol addition of the wild-type construct. However, mutation of the ABCA1LXR-binding site caused these responses to cease. The conclusion was that the presence of statin or cholesterol influenced ABCA1 transcription via an LXR ligand, and not through a SREBP-2/ABCA1-promoter binding mechanism.

The study also identified SREBP-2 as positive regulator of ABCA1 expression by promoting oxysterol ligand expression, thus activating LXR. However, a recent ABCA1 antibody study identified microRNA fragments embedded in non-coding regions of the SREBP-2 gene, which inhibited ABCA1 expression, confirming SREBP-2 also has a direct inhibitory effect. We at Novus Biologicals have many ABCA1 antibody products on our antibody database.