Int J Biol Sci 2009; 5(7):637-646. doi:10.7150/ijbs.5.637 This issue Cite

Research Paper

An apoA-I mimetic peptide facilitates off-loading cholesterol from HDL to liver cells through scavenger receptor BI

Xuelei Song, Paul Fischer, Xun Chen, Charlotte Burton, Jun Wang

Merck Research Laboratories, Rahway, New Jersey 07065, USA

Citation:
Song X, Fischer P, Chen X, Burton C, Wang J. An apoA-I mimetic peptide facilitates off-loading cholesterol from HDL to liver cells through scavenger receptor BI. Int J Biol Sci 2009; 5(7):637-646. doi:10.7150/ijbs.5.637. https://www.ijbs.com/v05p0637.htm
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Abstract

Apolipoprotein A-I (apoA-I) mimetic peptides have been pursued as new therapeutic agents for the treatment of atherosclerosis, yet their precise mechanism responsible for atheroprotection remains unclear. Like apoA-I itself, most of these peptides are capable of stimulating cholesterol efflux from macrophages or foam cells, and some of them stimulate lecithin cholesterol acyltransferase (LCAT) activity in the reverse cholesterol transport (RCT) pathway. However, the ability of mimetic peptides to deliver cholesterol into hepatocytes (off-loading), the last step of the RCT pathway, has not been demonstrated. In this study, we compared a mimetic peptide D-4F to purified apoA-I, to address the role that mimetics play during the off-loading process. Both D-4F and apoA-I formed spherical nano-particles when reconstituted with cholesteryl ester and phospholipids. Compared to apoA-I, D-4F particles were 20 times more efficient in off-loading cholesterol to HepG2 hepatocytes with an apparent Kt (transport) of 0.74 μg/mL. Furthermore, D-4F also facilitated cholesteryl ester offloading from HDL particles into HepG2 cells when it was pre-incubated with these HDL particles. Using an inducible HEK293 cell line, we demonstrated that these nano-particles were able to be taken up through SR-BI, a HDL selective receptor. Cholesterol uptake by HepG2 cells was completely blocked by a neutralizing monoclonal antibody against SR-BI, demonstrating that D-4F particles, similar to HDL, specifically off-loaded cholesterol through SR-BI. Overall our data provides evidence that D-4F is capable of mimicking apoA-I to form HDL-like particles, and off-loads cholesterol for catabolism and excretion, thus completing RCT.

Keywords: HDL, SR-BI, apolipoprotein, RCT, D-4F, mimetics


Citation styles

APA
Song, X., Fischer, P., Chen, X., Burton, C., Wang, J. (2009). An apoA-I mimetic peptide facilitates off-loading cholesterol from HDL to liver cells through scavenger receptor BI. International Journal of Biological Sciences, 5(7), 637-646. https://doi.org/10.7150/ijbs.5.637.

ACS
Song, X.; Fischer, P.; Chen, X.; Burton, C.; Wang, J. An apoA-I mimetic peptide facilitates off-loading cholesterol from HDL to liver cells through scavenger receptor BI. Int. J. Biol. Sci. 2009, 5 (7), 637-646. DOI: 10.7150/ijbs.5.637.

NLM
Song X, Fischer P, Chen X, Burton C, Wang J. An apoA-I mimetic peptide facilitates off-loading cholesterol from HDL to liver cells through scavenger receptor BI. Int J Biol Sci 2009; 5(7):637-646. doi:10.7150/ijbs.5.637. https://www.ijbs.com/v05p0637.htm

CSE
Song X, Fischer P, Chen X, Burton C, Wang J. 2009. An apoA-I mimetic peptide facilitates off-loading cholesterol from HDL to liver cells through scavenger receptor BI. Int J Biol Sci. 5(7):637-646.

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