文章基本信息

标题：The Mechanism of Action of Bufalin in Inhibition of Lipid Droplet Accumulation in Mouse Macrophages
本地全文：下载
作者：Keisuke Kobayashi ; Taichi Ohshiro ; Daisuke Matsuda 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2013
卷号：36
期号：3
页码：364-369
DOI：10.1248/bpb.b12-00722
出版社：The Pharmaceutical Society of Japan
摘要：A cardiotonic glycoside, bufalin, originally isolated from the dried white venom of Chinese toad Bufo gargarizans , was found to inhibit lipid droplet accumulation in mouse macrophages. Bufalin selectively inhibited synthesis of [¹⁴C]cholesteryl ester (CE), a main component of lipid droplet, from [¹⁴C]oleic acid and [¹⁴C]cholesterol with IC₅₀ values of 8.6 µ M and 10 µ M , respectively. The postlysosomal metabolism of cholesterol to CE in macrophages was also inhibited by the compound with a similar IC₅₀ value of 13.2 µ M . However, the compound exhibited almost no effect on acyl-CoA : cholesterol acyltransferase, a key enzyme in CE synthesis localized in the endoplasmic reticulum (ER). From the fluorescent microscopic observation of cellular lipids, bufalin-treated macrophages increased the accumulation of free cholesterol in lysosomes and caused to enlarge the shape and volume of lysosomes as well as pregnenolone-treated macrophages. These findings suggest that bufalin inhibited the postlysosomal metabolism of cholesterol, leading to a reduction of lipid droplets in mouse macrophages without cytotoxicity.
关键词：lipid droplet accumulation;cholesteryl ester;bufalin