Vitamin D Receptor As an Intestinal Bile Acid Sensor
2002; American Association for the Advancement of Science; Volume: 296; Issue: 5571 Linguagem: Inglês
10.1126/science.1070477
ISSN1095-9203
AutoresMakoto Makishima, Timothy T. Lu, Wen Xie, G. Kerr Whitfield, Hideharu Domoto, Ronald M. Evans, Mark R. Haussler, David J. Mangelsdorf,
Tópico(s)Pancreatitis Pathology and Treatment
ResumoThe vitamin D receptor (VDR) mediates the effects of the calcemic hormone 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]. We show that VDR also functions as a receptor for the secondary bile acid lithocholic acid (LCA), which is hepatotoxic and a potential enteric carcinogen. VDR is an order of magnitude more sensitive to LCA and its metabolites than are other nuclear receptors. Activation of VDR by LCA or vitamin D induced expression in vivo of CYP3A, a cytochrome P450 enzyme that detoxifies LCA in the liver and intestine. These studies offer a mechanism that may explain the proposed protective effects of vitamin D and its receptor against colon cancer.
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