QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal 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 Google Scholar Google Scholar Articles by Hayashi, I. Articles by Kim, Y.-I. Search for Related Content PubMed PubMed Citation Articles by Hayashi, I. Articles by Kim, Y.-I.

---

Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Folate Deficiency Induces Cell-Specific Changes in the Steady-State Transcript Levels of Genes Involved in Folate Metabolism and 1-Carbon Transfer Reactions in Human Colonic Epithelial Cells¹

² Department of Nutritional Sciences and ³ Department of Medicine, University of Toronto, Toronto, Ontario, Canada, M5S 1A8; ⁴ Clinical Epidemiology Unit, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada, M4N 3M5; and ⁵ Division of Gastroenterology, St. Michael's Hospital, Toronto, Ontario, Canada, M5B 1W8

^* To whom correspondence should be addressed. E-mail: youngin.kim{at}utoronto.ca.

Intracellular folate homeostasis is essential for the 1-carbon transfer reactions necessary for DNA synthesis and biological methylation reactions in colonic epithelial cells. Perturbed 1-carbon transfer reactions resulting from folate depletion predispose normal colonic epithelial cells to neoplastic transformation while inhibiting the growth of colon cancer cells. Using an in vitro model of folate deficiency, we determined the effects of folate deficiency on the steady-state transcript levels of genes involved in intracellular folate metabolism and 1-carbon transfer reactions in HCT116 and Caco2 human colon adenocarcinoma cells. In HCT116 cells, folate depletion was associated with changes in transcript levels of genes favoring increased folate uptake and intracellular folate retention, the provision of metabolically more effective substrates for folate-dependent enzymes, and reduced folate hydrolysis and efflux. In HCT116 cells, folate depletion was associated with changes in transcript levels of genes favoring the preferential shuttling of the flux of 1-carbon units to the methionine cycle over the nucleotide synthesis pathway. In Caco2 cells, some adaptive responses in response to folate depletion were not as apparent as in HCT116 cells, and in some cases, the direction of change was counterintuitive. In Caco2 cells, the metabolic priority in response to folate depletion was to shuttle the available folate pools to the nucleotide biosynthesis pathway at the expense of biological methylation reactions. In both HCT116 and Caco2 cells, folate depletion was associated with the conservation of the existing pattern and extent of DNA methylation.

This article has been cited by other articles:

				M. Jing, G. B. Tactacan, J. C. Rodriguez-Lecompte, A. Kroeker, and J. D. House Molecular cloning and tissue distribution of reduced folate carrier and effect of dietary folate supplementation on the expression of reduced folate carrier in laying hens Poult. Sci., September 1, 2009; 88(9): 1939 - 1947. [Abstract] [Full Text] [PDF]

				J. C. Waller, T. A. Akhtar, A. Lara-Nunez, J. F. Gregory III, R. P. McQuinn, J. J. Giovannoni, and A. D. Hanson Developmental and Feedforward Control of the Expression of Folate Biosynthesis Genes in Tomato Fruit Mol Plant, August 3, 2009; (2009) ssp057v1. [Abstract] [Full Text] [PDF]

				K. Loizeau, V. De Brouwer, B. Gambonnet, A. Yu, J.-P. Renou, D. Van Der Straeten, W. E. Lambert, F. Rebeille, and S. Ravanel A Genome-Wide and Metabolic Analysis Determined the Adaptive Response of Arabidopsis Cells to Folate Depletion Induced by Methotrexate Plant Physiology, December 1, 2008; 148(4): 2083 - 2095. [Abstract] [Full Text] [PDF]