| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received November 21, 2001
Accepted after revision December 4, 2001
1 Epithelial Function and Development Group, Department of Veterinary Preclinical Science, University of Liverpool, UK
2 Epithelial Function and Development Group, Department of Veterinary Preclinical Science, University of Liverpool, Crown Street, Liverpool L69 7ZJ, UK
* To whom correspondence should be addressed. E-mail: spsb{at}liverpool.ac.uk..
Butyrate is the principal source of energy for colonic epithelial cells, and has profound effects on their proliferation, differentiation and apoptosis. Transport of butyrate across the colonocyte luminal membrane is mediated by the monocarboxylate transporter 1 (MCT1). We have examined the regulation of expression of human colonic MCT1 by butyrate, in cultured colonic epithelial cells (AA/C1). Treatment with sodium butyrate (NaBut) resulted in a concentration- and time-dependent upregulation of both MCT1 mRNA and protein. At 2 mM butyrate, the magnitude of induction of mRNA (5.7-fold) entirely accounted for the 5.2-fold increase in protein abundance, and was mediated by both activation of transcription and enhanced mRNA stability. The other monocarboxylates found naturally in the colon, acetate and propionate, had no effect. The properties of butyrate uptake by AA/C1 cells were characteristic of MCT1. Induction of the MCT1 protein resulted in a corresponding increase in the maximal rate of butyrate transport. The Vmax for uptake of [U-14C]butyrate was increased 5-fold following pre-incubation with 2 mM NaBut, with no significant change in the apparent Km. In conclusion, this study is the first to show substrate-induced regulation of human colonic MCT1. The basis of this regulation is a butyrate-induced increase in MCT1 mRNA abundance, resulting from the dual control of MCT1 gene transcription and stability of the MCT1 transcript. We suggest that butyrate-induced increases in the expression and hence activity of MCT1 serve as a mechanism to maximise intracellular availability of butyrate, to act both as a source of energy and to influence processes maintaining cellular homeostasis in the colonic epithelium.
This article has been cited by other articles:
|
|
 |
|
  L. C. LaPointe, R. Dunne, G. S. Brown, D. L. Worthley, P. L. Molloy, D. Wattchow, and G. P. Young Map of differential transcript expression in the normal human large intestine Physiol Genomics, October 8, 2008; 33(1): 50 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hashimoto, R. Hussien, S. Oommen, K. Gohil, and G. A. Brooks Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis FASEB J, August 1, 2007; 21(10): 2602 - 2612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Graham, I. Gatherar, I. Haslam, M. Glanville, and N. L. Simmons Expression and localization of monocarboxylate transporters and sodium/proton exchangers in bovine rumen epithelium Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R997 - R1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Kirat, J. Masuoka, H. Hayashi, H. Iwano, H. Yokota, H. Taniyama, and S. Kato Monocarboxylate transporter 1 (MCT1) plays a direct role in short-chain fatty acids absorption in caprine rumen J. Physiol., October 15, 2006; 576(2): 635 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Kirat and S. Kato Monocarboxylate transporter 1 (MCT1) mediates transport of short-chain fatty acids in bovine caecum Exp Physiol, September 1, 2006; 91(5): 835 - 844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Roy, C. L. Kien, L. Bouthillier, and E. Levy Short-Chain Fatty Acids: Ready for Prime Time? Nutr Clin Pract, August 1, 2006; 21(4): 351 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Cuff, S. P. Shirazi-Beechey, P. K Dudeja, J. Malakooti, and K. Ramaswamy The Human Monocarboxylate Transporter MCT1: Gene Structure and Regulation Am J Physiol Gastrointest Liver Physiol, November 1, 2005; 289(5): G977 - G977. [Full Text] [PDF]
|
|
|
|
|
|
C. Hadjiagapiou, A. Borthakur, R. Y. Dahdal, R. K. Gill, J. Malakooti, K. Ramaswamy, and P. K. Dudeja Role of USF1 and USF2 as potential repressor proteins for human intestinal monocarboxylate transporter 1 promoter Am J Physiol Gastrointest Liver Physiol, June 1, 2005; 288(6): G1118 - G1126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Vidyasagar, C. Barmeyer, J. Geibel, H. J. Binder, and V. M. Rajendran Role of short-chain fatty acids in colonic HCO3 secretion Am J Physiol Gastrointest Liver Physiol, June 1, 2005; 288(6): G1217 - G1226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hashimoto, N. Kambara, R. Nohara, M. Yazawa, and S. Taguchi Expression of MHC-{beta} and MCT1 in cardiac muscle after exercise training in myocardial-infarcted rats J Appl Physiol, September 1, 2004; 97(3): 843 - 851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Alrefai, S. Tyagi, R. Gill, S. Saksena, C. Hadjiagapiou, F. Mansour, K. Ramaswamy, and P. K. Dudeja Regulation of butyrate uptake in Caco-2 cells by phorbol 12-myristate 13-acetate Am J Physiol Gastrointest Liver Physiol, February 1, 2004; 286(2): G197 - G203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Mengual, K. el Abida, N. Mouaffak, M. Rieu, and M. Beaudry Pyruvate shuttle in muscle cells: high-affinity pyruvate transport sites insensitive to trans-lactate efflux Am J Physiol Endocrinol Metab, December 1, 2003; 285(6): E1196 - E1204. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
