The Mechanism of Action of Bufalin in Inhibition of Lipid Droplet Accumulation in Mouse Macrophages

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概要

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• 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 µM and 10 µM, respectively. The postlysosomal metabolism of cholesterol to CE in macrophages was also inhibited by the compound with a similar IC50 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.

• 公益社団法人 日本薬学会の論文

著者

• Hong Bin

  National Key Laboratory For Screening Of New Microbial Drugs Institute Of Medical Biotechnology Chin

• Si Shuyi

  National Key Laboratory For Screening Of New Microbial Drugs Institute Of Medical Biotechnology Chin

• Matsuda Daisuke

  Graduate School Of Pharmaceutical Sciences Kitasato University

• Jiang Wei

  National Key Laboratory For Screening Of New Microbial Drugs Institute Of Medical Biotechnology Chin

• Ohshiro Taichi

  Graduate School Of Pharmaceutical Sciences Kitasato University

• Jiang Wei

  National Key Laboratory for Screening of New Microbial Drugs, Institute of Medical Biotechnology, Chinese Academy of Medical Science

• Tomoda Hiroshi

  Graduate School of Pharmaceutical Science, Kitasato University

• Kobayashi Keisuke

  Graduate School of Pharmaceutical Sciences, Kitasato University

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