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Cholesterol modulates human intestinal sodium-dependent bile acid transporter
Waddah A Alrefai1, Zaheer Sarwar, Sangeeta Tyagi
1Section of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois at Chicago and Jesse Brown Veteran Affairs Medical Center, Medical Research Service (600/151 820 South Damen Ave., Chicago, Illinois 60612, USA. walrefai@uic.edu
American Journal of Physiology. Gastrointestinal and Liver Physiology
|December 18, 2004
Summary
Cholesterol directly impacts bile acid absorption by inhibiting the ileal apical sodium-dependent bile acid transporter (ASBT). This finding reveals a novel regulatory mechanism crucial for maintaining cholesterol homeostasis.
Area of Science:
- Biochemistry
- Molecular Biology
- Gastroenterology
Background:
- Bile acid absorption via the ileal apical sodium-dependent bile acid transporter (ASBT) is vital for cholesterol homeostasis.
- The direct molecular mechanisms by which cholesterol influences human ASBT function and expression remain unclear.
Purpose of the Study:
- To establish a suitable in vitro model for studying human ASBT function and its regulation by cholesterol.
- To investigate the direct effects of cholesterol on ASBT activity and expression in a human intestinal cell line.
Main Methods:
- Utilized Caco-2 cell monolayers to measure sodium-dependent 3H-taurocholic acid uptake, assessing bile acid transport.
- Quantified human ASBT (hASBT) mRNA levels using real-time PCR.
- Assessed hASBT promoter activity via transient transfection and luciferase assays.
Main Results:
- Caco-2 cells provided a validated model for ASBT function and regulation studies.
- 25-Hydroxycholesterol significantly inhibited ASBT-mediated bile acid uptake by decreasing transporter Vmax.
- Inhibition of ASBT activity correlated with reduced hASBT mRNA levels and promoter activity.
Conclusions:
- Cholesterol directly inhibits human ASBT function and expression in intestinal cells.
- This cholesterol-induced regulation of ASBT plays a significant role in maintaining the body's cholesterol homeostasis.