Probucol Enhances the Expression of Human Hepatic Scavenger Receptor Class B Type I, Possibly Through a Species-Specific Mechanism
- 1 November 2005
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 25 (11), 2422-2427
- https://doi.org/10.1161/01.atv.0000185834.98941.3d
Abstract
Objective— Scavenger receptor class B type I (SR-BI) is a major receptor for high-density lipoproteins (HDL) in the liver, which is the terminus of reverse cholesterol transport. Overexpression of SR-BI attenuated experimental atherosclerosis in murine models, concomitant with a reduction in plasma HDL-cholesterol levels. Probucol is known to be a potent hypolipidemic drug to regress xanthoma formation and carotid atherosclerosis in conjunction with a marked reduction in HDL-cholesterol levels. The aim of the present study was to know the effect of probucol on the expression of SR-BI and the underlying mechanism. Methods and Results— We found that probucol increased the expression of SR-BI proteins in in vitro human liver cells and an in vivo rabbit model, but not in wild-type C57Bl6 mice. The decay curve of SR-BI protein was markedly retarded in probucol-treated HepG2 cells in the presence of cycloheximide, indicating that probucol may stabilize human SR-BI protein. To determine the underlying mechanism for the observed species-specific effect, we conducted the following host-swap experiments, in which SR-BI was transfected or expressed in heterologous cells or hosts. Probucol did not increase human SR-BI protein in the liver of transgenic mice carrying the entire human SR-BI genome. Although probucol could stabilize even murine SR-BI, when transfected into a human cell line, HepG2, human SR-BI was not stabilized in a mouse hepatoma cell line, Hepa 1-6, treated with probucol. Conclusion— Probucol enhances hepatic SR-BI protein expression, possibly through species-specific stabilization of the protein.Keywords
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