Metabolic fate of pancreas-derived cholesterol esterase in intestine: an in vitro study using Caco-2 cells.
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.
Huang
Y
Y
Department of Pathology and Laboratory Medicine, University of Cincinnati, College of Medicine, OH 45267-0529.
Hui
D Y
DY
D000230:Adenocarcinoma; D000818:Animals; D001646:Bile / Q000378:metabolism; D001692:Biological Transport; D002738:Chloroquine / Q000494:pharmacology; D002788:Cholesterol Esters / Q000378:metabolism; D003110:Colonic Neoplasms; D006801:Humans; D007422:Intestines / Q000201:enzymology*; D007700:Kinetics; D010179:Pancreas / Q000201:enzymology*; D002787:Sterol Esterase / Q000378:metabolism*; D013552:Swine; D014357:Trypsin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002788:Cholesterol Esters; D002738:Chloroquine; D002787:Sterol Esterase; D014357:Trypsin