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Effect Of Folate Oversupplementation On Folate Uptake By Human Intestinal And Renal Epithelial Cells.

B. Ashokkumar, Zainab M. Mohammed, N. Vaziri, H. Said
Published 2007 · Medicine, Biology

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BACKGROUND Folic acid [corrected] plays an essential role in cellular metabolism. Its deficiency can lead to neural tube defects. However, optimization of body folate homeostasis can reduce the incidence of neural tube defects and may decrease the risk of Alzheimer and cardiovascular diseases and cancer. Hence, food fortification and intake of supplemental folate are widespread. OBJECTIVE We examined the effects of long-term folate oversupplementation on the physiologic markers of intestinal and renal folate uptake processes. DESIGN Human-derived intestinal Caco-2 and renal HK-2 epithelial cells were maintained (5 generations) in a growth medium oversupplemented (100 micromol folic acid/L) or maintained under sufficient conditions (0.25 and 9 micromol folic acid/L). RESULTS Carrier-mediated uptake of (3)H-folic acid (2 micromol/L) at buffer pH 5.5 (but not buffer pH 7.4) by Caco-2 and HK-2 cells maintained under the folate-oversupplemented condition was significantly (P<0.01) and specifically lower than in cells maintained under the folate-sufficient condition. This reduction in folic acid uptake was associated with a significant decrease in the protein and mRNA levels of the human reduced-folate carrier (hRFC) and a decrease in the activity of the hRFC promoter. It was also associated with a decrease in mRNA levels of the proton-coupled folate transporter/heme carrier protein 1 (PCFT/HCP1) and folate receptor (FR). CONCLUSIONS Long-term oversupplementation with folate leads to a specific and significant down-regulation in intestinal and renal folate uptake, which is associated with a decrease in message levels of hRFC, PCFT/HCP1, and FR. This regulation appears to be mediated via a transcriptional mechanism, at least for the hRFC system.
This paper references
10.1016/S0009-2797(98)00038-6
Determination of folate transport pathways in cultured rat proximal tubule cells.
P. K. Sikka (1998)
10.1146/ANNUREV.PHYSIOL.66.032102.144611
Recent advances in carrier-mediated intestinal absorption of water-soluble vitamins.
H. Said (2004)
10.1006/MGME.2000.3027
Folic acid: nutritional biochemistry, molecular biology, and role in disease processes.
M. Lucock (2000)
10.1152/AJPCELL.00594.2005
Role of reduced folate carrier in intestinal folate uptake.
K. Balamurugan (2006)
10.1146/ANNUREV.NUTR.19.1.91
Carrier-mediated membrane transport of folates in mammalian cells.
F. Sirotnak (1999)
10.1042/BJ20040414
Roles of USF, Ikaros and Sp proteins in the transcriptional regulation of the human reduced folate carrier B promoter.
Mingjun Liu (2004)
10.1093/JN/129.6.1204
High dietary folate supplementation affects gestational development and dietary protein utilization in rats.
M. Achón (1999)
10.1542/PEDS.109.5.904
Occurrence of omphalocele in relation to maternal multivitamin use: a population-based study.
L. Botto (2002)
10.1158/1055-9965.EPI-152CO
Folate supplementation: too much of a good thing?
C. Ulrich (2006)
10.1093/JNCI/59.1.221
One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice.
J. Fogh (1977)
10.1093/JN/127.6.1137
Folate transport proteins mediate the bidirectional transport of 5-methyltetrahydrofolate in cultured human proximal tubule cells.
K. M. Morshed (1997)
Enterocyte-like differentiation and polarization of the human colon carcinoma cell line Caco-2 in culture
M. Pinto (1983)
10.1093/JN/133.6.1961S
Folic acid supplements and fortification affect the risk for neural tube defects, vascular disease and cancer: evolving science.
L. Bailey (2003)
10.1074/JBC.M008074200
The Basal Promoters for the Human Reduced Folate Carrier Gene Are Regulated by a GC-box and a cAMP-response Element/AP-1-like Element
J. Whetstine (2001)
10.1146/ANNUREV.NU.16.070196.000445
Folic acid and the prevention of birth defects.
C. Butterworth (1996)
Colorectal cancer and folate status: a nested case-control study among male smokers.
S. Glynn (1996)
10.1093/AJCN/84.4.680
The dubious use of vitamin-mineral supplements in relation to cardiovascular disease.
D. Mccormick (2006)
10.1016/0006-2952(86)90458-2
Properties of a folate binding protein (FBP) isolated from porcine kidney.
B. Kamen (1986)
10.1002/jcp.10324
Folate uptake in the human intestine: Promoter activity and effect of folate deficiency
V. S. Subramanian (2003)
Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues.
S. Weitman (1992)
10.1152/AJPRENAL.1992.263.5.F841
Folate transport and binding by cultured human proximal tubule cells.
K. McMartin (1992)
10.1042/BJ20020512
The human reduced folate carrier gene is ubiquitously and differentially expressed in normal human tissues: identification of seven non-coding exons and characterization of a novel promoter.
J. Whetstine (2002)
10.2174/1389200024605163
Physiology of folic acid in health and disease.
O. Stanger (2002)
10.1177/0891988703256052
Folic Acid Supplementation in Dementia: A Preliminary Report
B. R. Sommer (2003)
10.1016/0016-5085(90)90344-Z
The transport of vitamin B12 through polarized monolayers of Caco-2 cells.
C. Dix (1990)
10.1016/S0016-5085(97)70215-4
The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis.
B. Lashner (1997)
10.7326/0003-4819-94-2-283_2
Modern nutrition in health and disease
R. S. Goodhart (1980)
10.1016/S0300-9084(86)80177-8
The human colon carcinoma cell lines HT-29 and Caco-2: two in vitro models for the study of intestinal differentiation.
M. Rousset (1986)
10.1016/0005-2736(90)90362-R
Carrier affinity as a mechanism for the pH-dependence of folate transport in the small intestine.
J. Mason (1990)
10.1016/j.cell.2006.09.041
Identification of an Intestinal Folate Transporter and the Molecular Basis for Hereditary Folate Malabsorption
A. Qiu (2006)
10.1152/AJPRENAL.00014.2001
Extracellular glutathione peroxidase is secreted basolaterally by human renal proximal tubule cells.
J. Whitin (2002)
10.3181/00379727-196-43215
Analysis of the pH Dependence of Folate Binding and Transport by Rat Kidney Brush Border Membrane Vesicles
S. Bhandari (1991)
10.1093/JN/134.5.1130
Folic acid supplementation for 4 weeks affects liver morphology in aged rats.
María Roncalés (2004)
10.1093/JN/136.1.189
Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women.
A. Troen (2006)
10.2165/00128072-200002060-00003
Primary Prevention of Neural-Tube Defects and Some Other Major Congenital Abnormalities
A. Czeizel (2000)
The effect of folate supplementation on the risk of cancer or dysplasia in ulcerative colitis
BA Lashner (1997)



This paper is referenced by
10.1007/s11010-015-2577-x
Increased synthesis of folate transporters regulates folate transport in conditions of ethanol exposure and folate deficiency
S. Thakur (2015)
Classical Antifolates: Synthesis of 5-Substituted, 6-Substituted and 7-Substituted Pyrrolo[2,3-d]Pyrimidines as Targeted Anticancer Therapies
Y. Wang (2013)
10.1152/ajpcell.00249.2008
Differentiation-dependent regulation of the intestinal folate uptake process: studies with Caco-2 cells and native mouse intestine.
V. S. Subramanian (2008)
10.1158/1055-9965.EPI-10-0151
A Candidate Gene Study of Folate-Associated One Carbon Metabolism Genes and Colorectal Cancer Risk
A. Levine (2010)
10.1016/j.clinthera.2010.02.008
Effects of folic acid supplementation on the pharmacokinetics and anticoagulant effect of warfarin: an open-label, prospective study of long-term administration in adults.
M. Muszkat (2010)
Optimizing the Pharmacology of Periconceptional and Prenatal Multivitamin Supplementation
Patricia Nguyen (2009)
10.1146/annurev-physiol-020911-153251
The intestinal absorption of folates.
M. Visentin (2014)
Factors Influencing the Input Side of Folate Nutrition
Yen-Ming Chan (2016)
10.1007/s00394-010-0094-y
Folates in bread: retention during bread-making and in vitro bioaccessibility
V. Öhrvik (2010)
10.1039/C5RA16175D
Enhanced efficacy of chemotherapeutic drugs against colorectal cancer using ligand-decorated self-breakable agents
M. Tsai (2015)
10.1016/j.jconrel.2014.05.014
Polysaccharide-based micro/nanohydrogels for delivering macromolecular therapeutics.
K. Ganguly (2014)
Folate Absorption Across the Colon: And the Modulation of Bacterial Folate Synthesis by Diet
S. Aufreiter (2012)
10.1111/anu.13023
The effect of dietary folic acid on flesh quality and muscle antioxidant status referring to Nrf2 signalling pathway in young grass carp (Ctenopharyngodon idella)
L. Shi (2020)
10.7298/X4959FPJ
INFLUENCE OF B-VITAMINS ON ONE-CARBON METABOLISM AND ASSOCIATIONS WITH CANCER RISK AND REPRODUCTIVE STATE
Sajin Bae (2017)
10.1002/bdd.653
Transport characteristics of L‐citrulline in renal apical membrane of proximal tubular cells
Keisuke Mitsuoka (2009)
10.1038/ejcn.2016.194
The adverse effects of an excessive folic acid intake
K. Patel (2017)
10.1017/S1751731113001213
Post-hatching ontogeny of intestinal proton-coupled folate transporter and reduced folate carrier in broiler chickens.
M. Jing (2013)
10.1681/ASN.2011070711
Folate receptor-targeted antioxidant therapy ameliorates renal ischemia-reperfusion injury.
Sarah F Knight (2012)
10.3945/ajcn.2008.26564
Unmetabolized folic acid and total folate concentrations in breast milk are unaffected by low-dose folate supplements.
L. Houghton (2009)
10.3390/brainsci7110149
Is High Folic Acid Intake a Risk Factor for Autism?—A Review
Darrell J. Wiens (2017)
10.1089/dna.2011.1576
Folate malabsorption and its influence on DNA methylation during cancer development.
A. Hamid (2012)
10.1152/AJPCELL.00468.2007
Apical membrane targeting and trafficking of the human proton-coupled transporter in polarized epithelia.
V. S. Subramanian (2008)
10.1201/B11562-6
Folic Acid and Pathogenesis of Cardiovascular Disease
James D House (2012)
International Journal of Nanomedicine Dovepress Open Access to Scientific and Medical Research Open Access Full Text Article
Yelda Buyru Özkurt ()
10.1201/B20045-10
Overview of Methods of Making Polyester Nano- and Microparticulate Systems for Drug Delivery
M. Kumar (2017)
10.1111/1471-0528.12592
An optimal periconception maternal folate status for embryonic size: the Rotterdam Predict study
EM Uitert (2014)
10.1002/iub.133
Folate status in various pathophysiological conditions
N. A. Wani (2008)
10.1111/j.1753-4887.2010.00279.x
Vitamin/mineral supplements: of questionable benefit for the general population.
D. Mccormick (2010)
10.3177/JNSV.57.203
Vitamin contents in rat milk and effects of dietary vitamin intakes of dams on the vitamin contents in their milk.
Mika Endo (2011)
10.3177/JNSV.60.1
More than 50% of pregnant Japanese women with an intake of 150 μg dietary folate per 1,000 kcal can maintain values above the cut-off.
K. Shibata (2014)
10.1007/S11703-010-1047-1
Effects of folic acid supplementation on growth performance and hepatic folate metabolism-related gene expressions in weaned piglets
B. Yu (2010)
Maternal One-carbon Nutrients Status and Effects on DNA Methylation and Hydroxymethylation in Newborn Infants
Lesley Plumptre (2016)
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