2005•Arteriosclerosis Thrombosis and Vascular BiologyRequires access
Probucol Enhances the Expression of Human Hepatic Scavenger Receptor Class B Type I, Possibly Through a Species-Specific Mechanism
Ken-ichiHirano, ChiakiIkegami, Ken-ichiTsujii, ZhongyanZhang, FumihikoMatsuura, YumikoNakagawa-Toyama, MasahiroKoseki, DaisakuMasuda, TakaoMaruyama, IichiroShimomura, YukihikoUeda, ShizuyaYamashita
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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 ...