Erickson S K, Van Zuiden P E
Department of Medicine, University of California, San Francisco, USA.
Lipids. 1995 Oct;30(10):911-5. doi: 10.1007/BF02537482.
Acyl CoA:cholesterol acyltransferase (EC2.3.1.26, ACAT), responsible for intracellular esterification of cholesterol, may play an important role in cholesterol trafficking within the cell, and thus, in maintenance of cellular cholesterol homeostasis. Bile acids are potential regulators of cholesterol trafficking in the liver. Therefore, the effect of bile salts on hepatic ACAT activity was studied in the perfused rat liver. ACAT activity was increased after liver perfusion with either taurocholate or taurochenodeoxycholate. However, addition of these bile salts at physiological concentrations in vitro had little effect on microsomal ACAT activity. The increase in hepatic ACAT activity due to perfusion with bile salts was accompanied by reduced accumulation of very low density lipoprotein cholesterol in the perfusate, but there was no effect on 3-hydroxy-3-methylglutaryl-CoA reductase activity. Hepatic ACAT activity was decreased after bile diversion for four hours in the intact animal. This treatment had no statistically significant effect on 3-hydroxy-3-methylglutaryl-CoA reductase activity. These data suggest that bile salts induce changes in hepatic compartmentation and traffic of cholesterol within the hepatocyte accompanied by response of ACAT activity to maintain cellular cholesterol homeostasis.
酰基辅酶A：胆固醇酰基转移酶（EC2.3.1.26，ACAT）负责细胞内胆固醇的酯化，可能在细胞内胆固醇转运中起重要作用，进而在维持细胞胆固醇稳态方面发挥作用。胆汁酸是肝脏中胆固醇转运的潜在调节因子。因此，在灌注大鼠肝脏中研究了胆盐对肝脏ACAT活性的影响。用牛磺胆酸盐或牛磺鹅去氧胆酸盐灌注肝脏后，ACAT活性增加。然而，在体外以生理浓度添加这些胆盐对微粒体ACAT活性影响很小。由于胆盐灌注导致的肝脏ACAT活性增加伴随着灌注液中极低密度脂蛋白胆固醇积累的减少，但对3-羟基-3-甲基戊二酰辅酶A还原酶活性没有影响。在完整动物中胆汁引流4小时后，肝脏ACAT活性降低。这种处理对3-羟基-3-甲基戊二酰辅酶A还原酶活性没有统计学上的显著影响。这些数据表明，胆盐诱导肝细胞内胆固醇的肝内分布和转运发生变化，同时ACAT活性做出反应以维持细胞胆固醇稳态。
