Huang Y, Hui D Y
Department of Pathology and Laboratory Medicine, University of Cincinnati, College of Medicine, OH 45267-0529.
J Lipid Res. 1990 Nov;31(11):2029-37.
Bile salt-stimulated cholesterol esterase is synthesized in the pancreatic acinar cells and is released into the intestinal lumen where it catalyzes cholesterol absorption. In the current study, Caco-2 cells were used as an in vitro model to study the interaction between the pancreatic cholesterol esterase with intestinal cells. Results showed that addition of increasing concentrations of cholesterol esterase in the incubation medium increased the uptake of micellar cholesteryl oleate by Caco-2 cells. The cholesterol esterase also increased the cellular uptake of the nonhydrolyzable cholesteryl linoleoyl ether. However, maximum uptake of the cholesteryl ether analog was 50% of that for cholesteryl oleate. The initial interaction of cholesterol esterase with Caco-2 cells was mediated by binding of the protein to a low affinity and high capacity binding site on the cell surface. Cholesterol esterase bound to the cell surface could be internalized via a monensin-sensitive mechanism. The cholesterol esterase taken up by the cells had a short residence time and was either degraded or was rapidly re-secreted from the cells. Chloroquine had no effect on the degradation or re-secretion of cholesterol esterase by Caco-2 cells, indicating that lysosomes were not involved with these processes. The cholesterol esterase taken up by the cells was not available to mediate further cholesterol uptake. These results indicated that the bile salt-stimulated cholesterol esterase secreted from pancreas could facilitate intestinal lipid absorption only transiently. The data suggest that the regulation of cholesterol esterase synthesis and secretion by the pancreas may be important for regulation of cholesterol absorption.
胆汁盐刺激的胆固醇酯酶在胰腺腺泡细胞中合成，并释放到肠腔中，在那里它催化胆固醇的吸收。在本研究中，Caco-2细胞被用作体外模型，以研究胰腺胆固醇酯酶与肠细胞之间的相互作用。结果表明，在孵育培养基中添加浓度不断增加的胆固醇酯酶可增加Caco-2细胞对胶态油酸胆固醇酯的摄取。胆固醇酯酶还增加了不可水解的亚油酰基胆固醇醚的细胞摄取。然而，胆固醇醚类似物的最大摄取量是油酸胆固醇酯的50%。胆固醇酯酶与Caco-2细胞的初始相互作用是通过该蛋白与细胞表面低亲和力、高容量结合位点的结合介导的。结合到细胞表面的胆固醇酯酶可通过莫能菌素敏感机制内化。细胞摄取的胆固醇酯酶停留时间短，要么被降解，要么迅速从细胞中重新分泌出来。氯喹对Caco-2细胞降解或重新分泌胆固醇酯酶没有影响，表明溶酶体不参与这些过程。细胞摄取的胆固醇酯酶无法介导进一步的胆固醇摄取。这些结果表明，胰腺分泌的胆汁盐刺激的胆固醇酯酶只能短暂促进肠道脂质吸收。数据表明，胰腺对胆固醇酯酶合成和分泌的调节可能对胆固醇吸收的调节很重要。
