Document Detail

Inhibition of butyrate uptake by the primary bile salt chenodeoxycholic acid in intestinal epithelial cells.
MedLine Citation:
PMID:  22552910     Owner:  NLM     Status:  Publisher    
Colorectal cancer 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) upon (14) C-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 (14) C-BT uptake by IEC-6 cells (IC(50)  = 120 µM) and, less potently, by Caco-2 cells (IC(50)  = 402 µM). The inhibitory effect of CDCA upon (14) C-BT uptake did not result from a decrease in cell proliferation or viability. In IEC-6 cells: (1) uptake of (14) C-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 (14) C-BT, (3) CDCA significantly increased the mRNA expression level of SMCT1, (4) inhibition of (14) C-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 µM) reduced this effect. In conclusion, CDCA is an effective inhibitor of (14) C-BT uptake in tumoral and non-tumoral intestinal epithelial cells, through inhibition of both H(+) -coupled monocarboxylate transporter 1 (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. © 2012 Wiley Periodicals, Inc.
Pedro Gonçalves; Telmo Catarino; Inês Gregório; Fátima Martel
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-2
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  -     ISSN:  1097-4644     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Porto, Portugal.
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