环缩酚酸肽类抗生素对酰基辅酶A：胆固醇酰基转移酶活性的抑制作用。

Inhibition of acyl-CoA: cholesterol acyltransferase activity by cyclodepsipeptide antibiotics.

作者信息

Tomoda H, Huang X H, Cao J, Nishida H, Nagao R, Okuda S, Tanaka H, Omura S, Arai H, Inoue K

机构信息

Research Center for Biological Function, Kitasato Institute, Tokyo, Japan.

出版信息

J Antibiot (Tokyo). 1992 Oct;45(10):1626-32. doi: 10.7164/antibiotics.45.1626.

DOI:10.7164/antibiotics.45.1626

PMID:1473990

Abstract

The effect was studied of the fungal cyclodepsipeptide antibiotics beauvericin and seven distinct enniatins on acyl-CoA: cholesterol acyltransferase (ACAT) activity. In an enzyme assay using rat liver microsomes, all the compounds were found to inhibit ACAT activity. The drug concentration that caused 50% inhibition (IC50 value) of the enzyme activity was determined to be 3.0 microM for beauvericin, indicating that the compound is one of the most potent ACAT inhibitors of microbial origin. Enniatins exhibited much higher IC50 values of 22 to 110 microM. More hydrophobic enniatins showed more potent inhibitory activity. Furthermore, the ACAT inhibitory activity was evaluated as inhibition of cholesteryl ester formation in a cell assay using J774 macrophages. Calculation of the ratio, CD50 value (the drug concentration causing 50% cell damage)/IC50 value of cholesteryl ester formation, indicated that beauvericin shows the highest specificity. These data indicate that beauvericin is one of the most potent and specific ACAT inhibitors of microbial origin.

摘要

研究了真菌环缩肽抗生素白僵菌素和七种不同的恩镰孢菌素对酰基辅酶A：胆固醇酰基转移酶（ACAT）活性的影响。在使用大鼠肝脏微粒体的酶测定中，发现所有化合物均抑制ACAT活性。导致酶活性50%抑制（IC50值）的药物浓度对于白僵菌素测定为3.0 microM，表明该化合物是微生物来源中最有效的ACAT抑制剂之一。恩镰孢菌素表现出高得多的IC50值，为22至110 microM。疏水性更强的恩镰孢菌素显示出更强的抑制活性。此外，在使用J774巨噬细胞的细胞测定中，将ACAT抑制活性评估为对胆固醇酯形成的抑制。计算CD50值（导致50%细胞损伤的药物浓度）/胆固醇酯形成的IC50值的比率，表明白僵菌素具有最高的特异性。这些数据表明，白僵菌素是微生物来源中最有效和特异性最强的ACAT抑制剂之一。