RESUMO
In the human intestinal content after a meal, cholesterol is dispersed in a complex mixture of emulsified droplets, vesicles, mixed micelles and precipitated material. The aim of this study was to determine the contribution of the main intestinal cholesterol transporters (NPC1L1, SR-BI) to the absorption processes, using different cholesterol-solubilizing donors. Cholesterol donors prepared with different taurocholate concentrations were added to an apical medium of differentiated TC7/Caco-2 cells. As the taurocholate concentrations increased, cholesterol donor size decreased (from 712 to 7 nm in diameter), which enhanced cholesterol absorption in a dose-dependent manner (38-fold). Two transport processes were observed: (1) absorption from large donors exhibited low-capacity transport with no noticeable transporter contribution; (2) efficient cholesterol absorption occurs from small lipid donors (Assuntos
Colesterol na Dieta/metabolismo
, Absorção Intestinal/fisiologia
, Proteínas de Membrana/fisiologia
, Receptores Depuradores Classe B/fisiologia
, Sequência de Bases
, Ácidos e Sais Biliares/fisiologia
, Linhagem Celular
, Primers do DNA
, Regulação da Expressão Gênica/fisiologia
, Humanos
, Proteínas de Membrana/genética
, Proteínas de Membrana/metabolismo
, Proteínas de Membrana Transportadoras
, Receptores Depuradores Classe B/genética
, Receptores Depuradores Classe B/metabolismo
, Solubilidade
RESUMO
A dose-dependent increase in cholesterol absorption was induced by glucose addition (0-75 mM) to the apical medium of TC7 cells, a well-characterized clone of Caco-2. The uptake into the cells and the secretion rate to the basolateral space were both enhanced by glucose and galactose. This up-regulation was suppressed by SGLT1 inhibition but not by GLUT2 inhibition. Cholesterol cell uptake was significantly decreased by PMA and increased by chelerythrine, with more pronounced changes in the presence of hexoses. Thus, the involvement of a protein kinase C signalling pathway was evidenced in the regulation processes of intestinal cholesterol absorption. In the presence of antibodies directed to hSR-BI cholesterol absorption was reduced by 40% and glucose or galactose no longer enhanced it. We suggest that glucose or galactose, through an interaction with SGLT1, activates a protein kinase C pathway that regulates the activity of one of the intestinal cholesterol transporters, namely hSR-BI.