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This Article Full Text Full Text (PDF) A corrigendum has been published All Versions of this Article: 295/3/C828    most recent 00249.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Subramanian, V. S. Articles by Said, H. M. Search for Related Content PubMed PubMed Citation Articles by Subramanian, V. S. Articles by Said, H. M.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Differentiation-dependent regulation of the intestinal folate uptake process: studies with Caco-2 cells and native mouse intestine

¹Departments of Medicine, Physiology, and Biophysics, University of California, Irvine, California; and ²Department of Veterans Affairs Medical Center, Long Beach, California

Submitted 8 May 2008 ; accepted in final form 18 July 2008

Differentiation of intestinal epithelial cells is accompanied by alterations in levels of expression of many genes, including those involved in nutrient uptake. Effects of differentiation of intestinal epithelial cells on the physiological and molecular parameters of the intestinal folate uptake process are not well characterized. To address this issue, we used two models, Caco-2 cells and native mouse intestine. Studies with Caco-2 cells showed a significant increase in the initial rate of carrier-mediated folic acid uptake during differentiation (i.e., as the cells transitioned from preconfluent to confluent and then to postconfluent stages). This increase was associated with an increase in the level of expression of the human reduced folate carrier (hRFC) and the human proton-coupled folate transporter (hPCFT) both at the protein and mRNA levels with differentiation; it was also associated with a significant increase in activity of the hRFC and hPCFT promoters. Studies with native mouse intestine showed a significantly higher folate uptake in villus compared with crypt cells, which was again associated with a significantly higher level of expression of the mouse RFC and PCFT at the protein and mRNA levels. Together, these studies demonstrate that the intestinal folate uptake process undergoes differentiation-dependent regulation and that this regulation is mediated via changes in the level of expression of both the RFC and PCFT. In addition, the studies suggest the possible involvement (at least in part) of a transcriptional mechanism(s) in this type of regulation of the intestinal folate uptake process.

transport; epithelial transport; reduced folate carrier; proton-coupled folate transporter

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