title: The mechanism of action of bufalin in inhibition of lipid droplet accumulation in mouse macrophages.
abstract: 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 [C]cholesteryl ester (CE), a main component of lipid droplet, from [C]oleic acid and [C]cholesterol with IC values of 8.6 µM and 10 µM, respectively. The postlysosomal metabolism of cholesterol to CE in macrophages was also inhibited by the compound with a similar IC value of 13.2 µM. 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.
authors: Graduate School of Pharmaceutical Sciences, Kitasato University, 5–9–1 Shirokane, Minato-ku, Tokyo 108–8641, Japan.
authors: Keisuke
authors: K
authors: Kobayashi
authors: Taichi
authors: T
authors: Ohshiro
authors: Daisuke
authors: D
authors: Matsuda
authors: Wei
authors: W
authors: Jiang
authors: Bin
authors: B
authors: Hong
authors: Shuyi
authors: S
authors: Si
authors: Hiroshi
authors: H
authors: Tomoda
mesh_terms: D000818:Animals; D002018:Bufanolides / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002788:Cholesterol Esters / Q000096:biosynthesis; D050356:Lipid Metabolism / Q000187:drug effects*; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice
chemical_list: D002018:Bufanolides; D002316:Cardiotonic Agents; D002788:Cholesterol Esters; C022777:bufalin