RESUMO
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 micrograms/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.
Assuntos
Apolipoproteína A-II/fisiologia , Apolipoproteína A-I/fisiologia , Colesterol/farmacocinética , Intestinos/citologia , Lipoproteínas HDL/fisiologia , Células Tumorais Cultivadas/metabolismo , Adenocarcinoma/química , Adenocarcinoma/metabolismo , Apolipoproteína A-I/farmacocinética , Apolipoproteína A-II/farmacocinética , Ligação Competitiva , Caprilatos/metabolismo , Radioisótopos de Carbono/farmacocinética , Diferenciação Celular , Neoplasias do Colo/química , Neoplasias do Colo/metabolismo , Humanos , Radioisótopos do Iodo/farmacocinética , Lipossomos/metabolismoRESUMO
Auditory and vestibular function was examined in 29 patients with unilateral sensorineural hearing loss to identify characteristic vestibulocochlear lesion patterns. In 45%, a vestibular lesion was found, of which 53% had a combined impairment of the cochlea and the ipsilateral posterior semicircular canal, possibly reflecting vascular disease in the common cochlear artery.