Inhibition of butyrate uptake by the primary bile salt chenodeoxycholic acid in intestinal epithelial cells

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Gonçalves P (Author) FMUP; Catarino, T (Author) Other; Gregorio, I (Author) Other; Martel, F (Author) FMUP

Journal

Title: Journal of Cellular Biochemistry

Vol. 113 No. 3

Pages: 2937-2947

ISSN: 0730-2312

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 14 Citations

Scopus - 19 Citations

Other information

Authenticus ID: P-002-6QQ

DOI: 10.1002/jcb.24172

Abstract (EN): Colorectal cancer (CRC) is one of the most common cancers worldwide. Epidemiological and experimental studies suggest that bile acids may play a role in CRC etiology. Our aim was to characterize the effect of the primary bile acid chenodeoxycholic acid (CDCA) upon14C-BT uptake in tumoral (Caco-2) and non-tumoral (IEC-6) intestinal epithelial cell lines. A 2-day exposure to CDCA markedly and concentration-dependently inhibited 14C-BT uptake by IEC-6 cells (IC50?=?120 mu M), and, less potently, by Caco-2 cells (IC50?=?402 mu M). The inhibitory effect of CDCA upon 14C-BT uptake did not result from a decrease in cell proliferation or viability. In IEC-6 cells: (1) uptake of 14C-BT involves both a high-affinity and a low-affinity transporter, and CDCA acted as a competitive inhibitor of the high-affinity transporter; (2) CDCA inhibited both Na+-coupled monocarboxylate cotransporter 1 (SMCT1)- and H+-coupled monocarboxylate transporter 1 (MCT1)-mediated uptake of 14C-BT; (3) CDCA significantly increased the mRNA expression level of SMCT1; (4) inhibition of 14C-BT uptake by CDCA was dependent on CaM, MAP kinase (ERK1/2 and p38 pathways), and PKC activation, and reduced by a reactive oxygen species scavenger. Finally, BT (5?mM) decreased IEC-6 cell viability and increased IEC-6 cell differentiation, and CDCA (100 mu M) reduced this effect. In conclusion, CDCA is an effective inhibitor of 14C-BT uptake in tumoral and non-tumoral intestinal epithelial cells, through inhibition of both H+-coupled MCT1- and SMCT1-mediated transport. Given the role played by BT in the intestine, this mechanism may contribute to the procarcinogenic effect of CDCA at this level. J. Cell. Biochem. 113: 29372947, 2012. (C) 2012 Wiley Periodicals, Inc.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11