HDL3-mediated cholesterol efflux from cultured enterocytes: The role of apoproteins A-I and A-II |
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Authors: | Gerhard Herold Uta Hesse Frank Wisst Carl Fahr Milena Fahr Gerhard Rogler Irmlind Geerling Eduard F Stange |
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Affiliation: | 1. Department of Internal Medicine I, University of Ulm, 89070, Ulm, Germany
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Abstract: | High density lipoproteins (HDL) were recently demonstrated in an enterocyte model (CaCo-2 cells) to mediate reverse cholesterol
transport by retroendocytosis. The present study was carried out to define the role of the major HDL apoproteins (apo) A-I
and apo A-II in this pathway. HDL3 was fractionated by heparin affinity chromatography into the two main fractions containing either apo A-I only (fraction
A) or both apo A-I and apo A-II (fraction B). In addition, liposomes were reconstituted from purified apo A-I or apo A-II
and dimyristoyl phosphatidylcholine. The cell binding properties and cholesterol efflux potential were studied in the lipoprotein
fractions and the liposomes. Both fractions exhibited similar maximal binding capacities of 4427 (A) and 5041 (B) ng/mg cell
protein, but their dissociation constants differed (40.5 and 167.7 μg/mL, respectively). Fraction A induced cholesterol efflux
and stimulated cholesterol synthesis more than did fraction B. Fraction A mobilized both cellular free and esterified cholesterol,
whereas fraction B preferentially mobilized cholesteryl esters. Liposomes, containing either apo A-I or apo A-II, showed specific
binding, endocytosis and endosomal transport, and were released as intact particles. Apo A-I liposomes also mediated cholesterol
efflux. In conclusion, there is evidence that the HDL3 subfractions A and B, as well as reconstituted liposomes containing either apo A-I or apo A-II, were specifically bound and
entered a retroendocytosis pathway which was directly linked to cholesterol efflux. Quantitatively, the apo A-I subfraction
appeared to play the dominant role in normal enterocytes. The apo A-II content of fraction B was related to the mobilization
of cholesteryl esters. |
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