Details

Autor(en) / Beteiligte

• Favari, Elda
• Zanotti, Ilaria
• Zimetti, Francesca
• Ronda, Nicoletta
• Bernini, Franco
• Rothblat, George H

Titel

Probucol inhibits ABCA1-mediated cellular lipid efflux

Ist Teil von

• Arteriosclerosis, thrombosis, and vascular biology, 2004-12, Vol.24 (12), p.2345-2350

Ort / Verlag

United States

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of lipids from cells to lipid-poor apolipoproteins. In this article, we characterize the effect of probucol on cellular ABCA1-mediated lipid efflux. Probucol inhibited cholesterol efflux up to 80% in J774 macrophages expressing ABCA1. In Fu5AH hepatoma cells that contain scavenger receptor class B, type I, but not functional ABCA1, we observed no effect of probucol on cholesterol efflux. Probucol inhibited cholesterol efflux from normal human skin fibroblasts but not from fibroblasts from a Tangier patient. Fluorescent confocal microscopy and biotinylation assay demonstrated that in J774 cells probucol impaired the translocation of ABCA1 from intracellular compartments to the plasma membrane. Probucol also inhibited the formation of an ABCA1-linked cholesterol oxidase sensitive plasma membrane domain. Consistent with the inhibitory effect on ABCA1 translocation to the plasma membrane, probucol reduced cell surface-specific [125I]-labeled apolipoprotein-AI binding. We conclude that probucol is an effective inhibitor of ABCA1-mediated cholesterol efflux without influencing scavenger receptor class B type I-mediated efflux. The inhibition of ABCA1 translocation to the plasma membrane may in part explain the reported in vivo high-density lipoprotein-lowering action of probucol.