Evidence for extralysosomal hydrolysis of high-density lipoprotein cholesteryl esters in rat hepatoma cells (Fu5AH): a model for delivery of high-density lipoprotein cholesterol.
Evidence for extralysosomal hydrolysis of high-density lipoprotein cholesteryl esters in rat hepatoma cells (Fu5AH): a model for delivery of high-density lipoprotein cholesterol.
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大鼠肝癌细胞（Fu5AH）中高密度脂蛋白胆固醇酯溶酶体外水解的证据：高密度脂蛋白胆固醇递送模型。
DOI：
10.1002/jcp.1041460104
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发表时间：
1991
影响因子：
5.6
通讯作者：
Hornick,CA
中科院分区：
文献类型：
--
作者：
DeLamatre,JG;Carter,RM;Hornick,CA
以大鼠肝癌细胞(Fu5AH)为模型，研究了不含apoE的高密度脂蛋白(HDLc)的净转运。用高密度脂蛋白孵育细胞的结果是：(1)无介质胆固醇和胆固醇酯浓度降低；(2)细胞甾醇合成减少；(3)细胞胆固醇酯合成增加。当细胞在胆固醇含量较低的培养液中孵育18小时时，高密度脂蛋白胆固醇酯的摄取增加。~3H-胆固醇酯标记的低密度脂蛋白与50μM氯喹或25μM莫能菌素共孵育后，细胞内游离胆固醇/胆固醇酯(FC/CE)同位素比值降低，表明胆固醇酯向游离胆固醇的转化受到抑制。相反，氯喹和莫能菌素不会改变~3H-CE高密度脂蛋白的细胞Fc/CE同位素比率。这一证据表明，酸性溶酶体胆固醇酯水解酶不能解释高密度脂蛋白-CE的水解。低密度脂蛋白和高密度脂蛋白的~3H-胆固醇酯生成的游离胆固醇在细胞内再酯化。在较高的高密度脂蛋白浓度(50μg/ml以上)下，高密度脂蛋白胆固醇酯的水解对氯喹很敏感。我们认为溶酶体外途径在高密度脂蛋白的代谢中起作用，在较高的高密度脂蛋白浓度下，溶酶体途径可能除了溶酶体外途径外还起作用。
Rat hepatoma cells (Fu5AH) were studied as a model for the net delivery of apoE‐free high‐density lipoprotein (HDL) cholesterol to a cell. Incubating cells with HDL results in (1) a decrease in both media‐free cholesterol and cholesteryl ester concentration; (2) decreased cell sterol synthesis; and (3) increased cell cholesteryl ester synthesis. HDL cholesteryl ester uptake is increased when cells are incubated for 18 hr in cholesterol poor media. Coincubation of3H‐cholesteryl ester‐labeled low‐density lipoprotein (LDL) with 50 μM chloroquine or 25 μM monensin results in a decrease in the cellular free cholesterol/cholesteryl ester (FC/CE) isotope ratio, indicating an inhibition in the conversion of cholesteryl ester to free cholesterol. In contrast, chloroquine and monensin do not alter the cellular FC/CE isotope ratio for3H‐CE HDL. This evidence indicates that acidic lysosomal cholesteryl ester hydrolase does not account for the hydrolysis of HDL‐CE. Free cholesterol generated from3H‐cholesteryl ester of both LDL and HDL is reesterified intracellularly. At higher HDL concentrations (above 50 μg/ml) HDL cholesteryl ester hydrolysis is sensitive to chloroquine. We propose that an extralysosomal pathway is operating in the metabolism of HDL cholesterol and that at higher HDL concentrations a lysosomal pathway may be functioning in addition to an extralysosomal pathway.