Rabbit aortic smooth muscle cells in culture were incubated with 0.04-500 M esterastin. Acid cholesteryl ester hydrolase (ACEH) and neutral cholesteryl ester hydrolase (NCEH) activities were inhibited to a comparable degree, with 50% inhibition occurring in the range of 0.4 M esterastin. Cells incubated with cholesteryl oleyl ether showed 50% inhibition of NCEH at 5.0 M, but no inhibition of ACEH over a concentration range of 0.2-20 M. This relative specificity of cholesteryl oleyl ether for NCEH can be employed to study the relative roles of ACEH vs. NCEH in preventing cellular cholesteryl ester accumulation.
Title: Effect of esterastin, an acid lipase inhibitor, on the free and esterified cholesterol contents of cultured aortic smooth muscle cells treated with LDL and cholesterol ester liquid crystals Ecsedi GG, Amanuma K, Imanaka T, Aoyagi T, Ohkuma S, Takano T Ref: Biochemistry International, 10:337, 1985 : PubMed
The effects of esterastin, an acid lipase inhibitor, on the free and esterified cholesterol contents of cultured smooth muscle cells from pig aorta were examined. The post-nuclear supernatant fraction of the cell homogenate showed maximum acid cholesterol esterase activity at pH 4.5, and 50% of this activity was inhibited by 0.31 microM esterastin. During a 48 h incubation with esterastin, the esterified cholesterol content of the cells increased to about 13 times that of control cells in the presence of low density lipoprotein and to 7 times that of control cells in the presence of cholesterol oleate liquid crystals. The ratio of esterified to free cholesterol also increased to about 5 times the control value in both conditions.
The effect of a fungal metabolite, esterastin, on lysosomal acid lipase purified from rabbit liver was studied. Esterastin inhibited the enzyme activity very strongly (IC50, about 80 nM). The inhibition of acid lipase by esterastin was competitive with respect to the substrate and the inhibition constant for esterastin was 90 nM. Esterastin was less inhibitory to other lipolytic enzymes, such as pancreatic lipase and carboxylesterase. Thus esterastin is a potent new inhibitor of lysosomal acid lipase.
2 lessTitle: Relative specificities of inhibition of acid cholesteryl ester hydrolase and neutral cholesteryl ester hydrolase in cultured rabbit aortic smooth muscle cells by esterastin and cholesteryl oleyl ether Morin RJ, Peng SK Ref: Biochimica & Biophysica Acta, 1004:139, 1989 : PubMed
Rabbit aortic smooth muscle cells in culture were incubated with 0.04-500 M esterastin. Acid cholesteryl ester hydrolase (ACEH) and neutral cholesteryl ester hydrolase (NCEH) activities were inhibited to a comparable degree, with 50% inhibition occurring in the range of 0.4 M esterastin. Cells incubated with cholesteryl oleyl ether showed 50% inhibition of NCEH at 5.0 M, but no inhibition of ACEH over a concentration range of 0.2-20 M. This relative specificity of cholesteryl oleyl ether for NCEH can be employed to study the relative roles of ACEH vs. NCEH in preventing cellular cholesteryl ester accumulation.
Title: Effect of esterastin, an acid lipase inhibitor, on the free and esterified cholesterol contents of cultured aortic smooth muscle cells treated with LDL and cholesterol ester liquid crystals Ecsedi GG, Amanuma K, Imanaka T, Aoyagi T, Ohkuma S, Takano T Ref: Biochemistry International, 10:337, 1985 : PubMed
The effects of esterastin, an acid lipase inhibitor, on the free and esterified cholesterol contents of cultured smooth muscle cells from pig aorta were examined. The post-nuclear supernatant fraction of the cell homogenate showed maximum acid cholesterol esterase activity at pH 4.5, and 50% of this activity was inhibited by 0.31 microM esterastin. During a 48 h incubation with esterastin, the esterified cholesterol content of the cells increased to about 13 times that of control cells in the presence of low density lipoprotein and to 7 times that of control cells in the presence of cholesterol oleate liquid crystals. The ratio of esterified to free cholesterol also increased to about 5 times the control value in both conditions.
The effect of a fungal metabolite, esterastin, on lysosomal acid lipase purified from rabbit liver was studied. Esterastin inhibited the enzyme activity very strongly (IC50, about 80 nM). The inhibition of acid lipase by esterastin was competitive with respect to the substrate and the inhibition constant for esterastin was 90 nM. Esterastin was less inhibitory to other lipolytic enzymes, such as pancreatic lipase and carboxylesterase. Thus esterastin is a potent new inhibitor of lysosomal acid lipase.
