期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 298, 期 3, 页码 G467-G473出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00360.2009
关键词
lipid rafts; (-)-epigallocatechin-3-gallate; hypercholesterolemia
资金
- National Institute of Diabetes and Digestive and Kidney Diseases [F32 DK79542, DK74459, DK71596]
- Crohn's and Colitis Foundation of America CCFA [1942]
Annaba F, Kumar P, Dudeja AK, Saksena S, Gill RK, Alrefai WA. Green tea catechin EGCG inhibits ileal apical sodium bile acid transporter ASBT. Am J Physiol Gastrointest Liver Physiol 298: G467-G473, 2010. First published January 7, 2010; doi: 10.1152/ajpgi.00360.2009.-Green tea catechins exhibit hypocholesterolemic effects probably via their inhibitory effects on intestinal bile acid absorption. Ileal apical sodium-dependent bile acid transporter (ASBT) is responsible for reabsorption of bile acids. The present studies were, therefore, designed to investigate the modulation of ASBT function and membrane expression by green tea catechins in human embryonic kidney HEK-293 cells stably transfected with ASBT-V5 fusion protein and intestinal Caco-2 monolayers. Our data showed that ASBT activity was significantly decreased by (-)-epigallocatechin-3-gallate ( EGCG) but not other green tea catechins. Inhibition of PKC, phosphatidylinositol 3-kinase, and MAPK-dependent pathways failed to block the reduction in ASBT activity by EGCG. Kinetics studies showed a significant decrease in the V-max of the transporter, whereas total ASBT content on the plasma membrane was unaltered by EGCG. Concomitant with the decrease in ASBT function, EGCG significantly reduced ASBT pool in the detergent-insoluble fraction, while increasing its presence in the detergent-soluble fraction of plasma membrane. Furthermore, EGCG decreased the association of ASBT with floating lipid raft fractions of cellular membrane on Optiprep density gradient. In conclusion, our data demonstrate a novel role of lipid rafts in the modulation of ASBT function by the dietary component EGCG, which may underlie the hypocholesterolemic effects of green tea.
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